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)

Acadesine (5-amino-4-imidazole carboxamide riboside) is a purine nucleoside analog that has been shown in animals to reduce myocardial ischemic injury by selectively increasing the availability of adenosine in ischemic tissues. Because patients undergoing coronary artery bypass graft (CABG) surgery are especially vulnerable to developing myocardial ischemia, we investigated whether perioperative use of this adenosine-regulating drug with potential anti-ischemic properties could modify the incidence and severity of perioperative myocardial ischemia. The goals of this study were to evaluate safety and the effects of acadesine on myocardial ischemia, left ventricular function, and, secondarily, on adverse clinical outcomes (myocardial infarction, heart failure, life-threatening dysrhythmias, and death) in patients undergoing CABG surgery. One hundred sixteen patients were randomized to receive one of three continuous intravenous dosing regimens (placebo [control] or one of two doses of acadesine [high- and low-dose infusion]) in double-blind fashion intraoperatively and in the early postoperative period (total infusion time was 7 h). Multidose cold crystalloid cardioplegia (each containing either acadesine or placebo) was used for myocardial protection. All were monitored for potentially drug-related adverse events and the presence of myocardial ischemia was assessed by continuous Holter electrocardiography (ECG) and transesophageal echocardiography (TEE). All patients received standardized anesthetic, surgical, and hemodynamic management during the intraoperative period. All research data (ECG, TEE, outcome data) were evaluated at the coordinating center (San Francisco) in blinded fashion to ensure that uniform data analysis criteria were employed. The administration of acadesine was safe: mild increases in plasma uric acid (a metabolite of acadesine) occurred only in patients receiving high doses (mean increase 1.6 +/- 0.2 mg/dL) and were without clinical sequelae. Before drug administration in the preoperative period (baseline), the incidence and severity of ECG ischemia did not differ among the three groups (placebo = 18%; low-dose = 14%; high-dose = 14%). During prebypass, the incidence of ECG ischemia was similar in all three groups (0%, 3%, 3%, respectively). The incidence of TEE ischemia was numerically lower in the two acadesine groups (high-dose = 6%, low-dose = 15%) than in the control group (19%), but this was not statistically significant (P = 0.22). During postbypass, the incidence of ECG ischemia was 11% in the high-dose group, 22% in the low-dose group, and 18% in the control group (P = 0.42), and TEE ischemia was similar in incidence in all groups (placebo = 29%; low dose = 27%; high-dose = 24%) (P = 0.86).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:An initial multicenter, randomized controlled trial on the safety and efficacy of acadesine in patients undergoing coronary artery bypass graft surgery. SPI Research Group. 797 87

Between January 1991 and June 1993, eleven children with anomalous origin of the left coronary artery from the pulmonary artery underwent direct aortic reimplantation of the left coronary artery at the German Heart Institute Berlin. The patients' ages ranged from 2.5 months to 10.5 years; six were infants. Three infants were intubated and their lungs ventilated before the operation, and one was resuscitated 2 days before the operation. The electrocardiograms of eight patients indicated deep Q waves. All but three of these patients had insufficient collaterals between the right and left coronary arteries. The entire group exhibited reduced left ventricular ejection fraction (minimum 15%) including mitral valve incompetence, which was moderate in six patients and severe in three. All six infants underwent emergency operations, and the remaining children, who were older, underwent elective operations involving moderate hypothermic perfusion and cold crystalloid cardioplegia. Aortic cross-clamping time ranged from 22 to 79 minutes (mean 54 minutes). A two-coronary artery system was established in all patients by direct reimplantation of the anomalous left coronary artery into the ascending aorta. Three patients who also exhibited severe mitral valve incompetence underwent modified Kay mitral valve annuloplasty. A delayed sternal closure procedure (closure performed 1 to 10 days after the operation) was used on eight patients. A 10-month-old patient was successfully treated after the operation with a centrifugal left heart assist device and a 9-year-old patient received extracorporeal membrane oxygenation because of severe heart failure. No postoperative deaths occurred. Left ventricular end-diastolic volume decreased dramatically after the operation and returned to near normal values 1 to 9 months postoperatively. At the same time, the preoperatively depressed left ventricular ejection fraction returned to normal and mitral valve incompetence decreased or vanished in eight patients. Color Doppler echocardiograms (eleven patients) and coronary angiograms (three patients) indicated that the reimplanted left coronary artery was patent in all eleven patients during the follow-up period. Reimplantation of the left coronary artery into the ascending aorta is an effective method of establishing a two-coronary artery system in children with anomalous origin of the left coronary artery from the pulmonary artery. Mitral valve annuloplasty is recommended for patients who also have severe mitral valve incompetence. Prolonged assisted circulation must be used in cases of severe postoperative heart failure.
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PMID:Anomalous origin of the left coronary artery from the pulmonary artery. Early results with direct aortic reimplantation. 1154 30

Heart failure is a syndrome characterized by the activation of neurohumoral mechanisms (sympathoadrenergic, renin-angiotensin, vasopressin) which cause peripheral vasoconstriction, sodium retention and myocardial hypertrophy. In acute myocardial disfunction these systems can play a critical role in patient survival, however, they can directly worsen myocardial function and patient prognosis on a long-term basis. Other neurohumoral systems activated in heart failure (atrial natriuretic factor, prostaglandins, dopamine) tend to counterbalance the vasoconstrictive, sodium retentive mechanisms. Though their secretion is increased in heart failure, it is however not sufficient, and peripheral vasoconstriction and sodium retention prevail. Moreover the role of local factors, such as tissue renin-angiotensin system, EDRF and endothelin secretion has been recently pointed out. Neurohumoral activation is directly related to the severity of the clinical and hemodynamic impairment and prognosis of the patient with heart failure. A thorough evaluation of the neurohumoral mechanisms is therefore of paramount importance for the assessment of patients with heart failure. Neurohumoral activation can be roughly assessed using some simple laboratory measurements: plasma sodium concentration, for example, is inversely related to the degree of activation of many neurohormones such as norepinephrine, angiotensin II, vasopressin and atrial natriuretic factor. The method most commonly used to assess neurohumoral activity relies on the direct measurement of the plasma concentrations. It must be noted, however, that plasma levels are critically dependent on many factors besides hormone secretion and metabolism. For example, 3-4 days on a low sodium diet or standing for at least 2 hours can increase plasma renin activity in a normal subject from 1.5 to 5-10 pg/ml/hr. Plasma concentrations of neurohormones are related to the factors controlling their secretion: for example, "normal" values of plasma renin activity in presence of fluid retention and edema are to be judged as excessively elevated. Autonomic nervous system activity can also be assessed studying reflexes in which this system is involved (orthostasis, cold pressor test, phenylephrine test...). Another method consists in the study of the spontaneous variability of some parameters controlled by this system, such as heart rate and blood pressure. The most reliable method is based on the power spectral analysis of heart rate variability. With this last method, a low frequency component depending mainly on sympathetic activity and an high frequency component depending on vagal activity can be identified in heart rate variability. Thus, complex phenomena such as sympatho-vagal balance can be easily studied through simple noninvasive tools.
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PMID:[Neurohormonal assessment in heart failure: from the sophisticated laboratory to practical indications]. 809 6

This review outlines the mechanisms of body temperature control and the validity of various sites of measurement of core temperature. The mechanism of fever in response to circulating endotoxins are discussed, and the roles of various peripherally generated pyrogenic cytokines are outlined together with the loci of their action in the brain. The cardiovascular consequences of exposure to heat, particularly the pooling of blood in the skin and the increase of heart rate due to heating of the sinoatrial node, are discussed. The consequences of blood pooling, such as syncope or diminished G tolerance, are very important. Heat exposure and exercise lead to complex circulatory interactions, such as a higher heart rate for a given exercise load in the heat compared with a cool environment. At high work loads there may be a relatively lower cardiac output in hot conditions. Blood lactate levels and rectal temperature tend to be higher in exercise in the heat than exercise in the cold. Fever causes a large renal vasodilation and hepatic vasodilation, which are humorally mediated and which effectively cause a splanchnic vascular shunt of some consequence if there is already heart failure or shock. Syncope during fever, endotoxin shock and the role of pyrogens in heat stroke are discussed.
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PMID:Some responses of the cardiovascular system to heat and fever. 819 89

Preweaning losses: During the period from September 1991 to August 1992, from 18021 piglets born alive 3417 died until weaning. Major causes of death were crushing by the sow, low birth weight, starvation, splay-leg disease and enteritis. Of these animals 51.6% died during the first three days of life. Mortality decreased during the preweaning period. Litters with more than 11 pigs had elevated death rates of piglets. Mortality was higher during the cold season (except January). Postweaning losses: During the postweaning period 6.4% of the weaned piglets were lost. Of these piglets 4.1% died and the remaining 2.3% were sold due to umbilical hernia. Diseases of the gastrointestinal tract were the main cause of death. Losses of gilts: During the one-year surveillance period 373 gilts were lost. Most of 18 deceased animals died from bleeding due to gastric ulcers and from purulent bronchopneumonia. 314 (91.1%) of the remaining 355 gilts were sold, the residual 9.9% of the animals were slaughtered mainly because of diseases of the musculoskeletal system. Losses of sows: In the breeding herd of 950 to 1035 animals, 35 sows died and 492 were culled in the course of one year. Most deaths resulted from cardiac failure and splenic torsion. Urogenital and locomotor diseases were the main reason for culling. The sows removed from the herd had produced an average of 3.6 litters, but 52.8% had produced no more than 3 litters. Losses of boars: During the survey 10 boars were slaughtered.
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PMID:[Causes of mortality in a swine breeding establishment]. 830 62

From March 1991 through July 1992, 1,001 patients having elective coronary artery bypass grafting were randomized to receive either continuous warm (> or = 35 degrees C) blood cardioplegia with systemic normothermia (> or = 35 degrees C) or intermittent cold (< or = 8 degrees C) oxygenated crystalloid cardioplegia and moderate systemic hypothermia (< or = 28 degrees C). Preoperative variables including age, sex, prior coronary bypass grafting, hypertension, prior myocardial infarction, diabetes, angina class, and preoperative heart failure class were similar in both groups, as were the intraoperative variables of number of coronary grafts, mammary artery use, and cardiopulmonary bypass time. Aortic cross-clamp time was significantly longer in the warm group (46 +/- 23 minutes versus 40 +/- 21 minutes). Most postoperative variables including mortality (warm, 1.0%, and cold, 1.6%), Q wave infarction (warm, 1.4%, and cold, 0.8%), and need of an intraaortic balloon pump (warm, 1.4%, and cold, 2.0%) were similar between groups. Total neurologic events (warm, 4.5%, and cold, 1.4%; p < 0.005) and perioperative strokes (warm, 3.1%, and cold, 1.0%; p < or = 0.02) were significantly higher in the warm group. Neurologic events included perioperative stroke (warm, 15 patients, and cold, 5 patients; p < 0.02), perioperative encephalopathy (warm, 2 patients, and cold, 1 patient), and delayed (> or = 3 in-hospital days) stroke (warm, 5 patients, and cold, 1 patient). All patients experiencing a stroke had a persistent neurologic deficit at the time of discharge. Encephalopathy resolved completely in all instances.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat. 784 93

A 64-year-old man was admitted to our hospital with complaints of chest pain on Sep. 26, 1991. ECG revealed myocardial infarction-like ST-elevation in II, III, aVF, V4, V5, and V6 but coronary angiography revealed no abnormal findings in the right and left coronary arteries, and no elevation of SGOT, LDH or CPK was found. Chest CT scan, UCG and chest MRI revealed a tumor invading into myocardium in the left cardiophrenic angle. Myocardial scintigraphy revealed a cold area in the inferior wall. Histologically, the tumor was squamous cell cancer. In spite of treatment, the patient died due to heart failure on Feb. 8, 1992. Myocardial metastasis showing a myocardial infarction-like ECG has been rarely reported.
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PMID:[A case of lung cancer with myocardial metastasis with ECG suggestive of myocardial infarction]. 833 49

Although enhanced sympathetic tone is a well-known component of the autonomic imbalance of heart failure, its influence on pulmonary vasomotility is undefined. We investigated the pulmonary circulation in 12 patients with congestive heart failure in NYHA functional class III and in a control group of 10 normal subjects. Sympathetic influence on pulmonary vessels was studied through adrenergic activation by the arithmetic test and the cold pressor test. A rubber balloon was distended in the inferior vena cava to reduce transpulmonary flow and its influence on vascular tone. In normal individuals the arithmetic test caused pulmonary vasodilation, probably because of the mechanical effect of a largely enhanced flow: in fact, caval obstruction unmasked a neurogenic vasoconstrictor response to the arithmetic test by simply reducing the amount of cardiac output increase. In patients with heart failure, cardiac output and pulmonary arteriolar resistance remained steady during the arithmetic test, no matter what the condition of the venous return was. The cold pressor test was always a vasoconstrictor stimulus, but only in normal subjects was vasoconstriction potentiated by reducing, with caval obstruction, transpulmonary flow and its vasodilatory influence. From these data an attenuation of the sympathetic influence on pulmonary vessels in congestive heart failure seems to be likely. This might be explained as the result of modifications of pulmonary vessels rather than of reduced sympathetic excitability since circulating catecholamine levels varied to similar extents in the two groups during the tests. In congestive heart failure interstitial edema and vascular wall imbibition might increase pulmonary vessel tone and decrease vascular receptor availability. Lower reactivity to sympathetic stimuli, particularly to the vasoconstrictor ones, would ensue.
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PMID:Control of pulmonary vasomotility in congestive heart failure. 844 98

Four patients with suprarenal coarctation of the abdominal aorta were managed from 1978 to 1993 (mean follow-up 8.75 years). Ages at the time of diagnosis were 2 months, 8 months, 4.5 years, and 15 years, respectively. Three children presented with severe hypertension, two of whom were in congestive heart failure, and the fourth child presented with a cold, ischemic leg. The 8-month-old patient had Williams syndrome (supravalvular aortic and pulmonic stenosis, bilateral renal artery stenosis and celiac artery occlusion, "elfin" facies, and mental retardation) and was treated nonoperatively. After 12 years of follow-up, he was given five medications to control hypertension, cardiac arrhythmias, and heart failure. Three patients with abdominal aortic coarctation were treated operatively and none died. Two patients underwent bypass grafting from the supraceliac aorta to the infrarenal aorta, with bilateral renal artery reconstruction in one. Postoperative arteriograms obtained 1 year or more after operation were normal in both cases. The 2-month-old patient underwent patch aortoplasty, with subsequent reoperation 1.5 years later for recurrent hypertension and heart failure with a bypass graft to the left kidney and removal of an infarcted right kidney. In all three patients, operative repair of the suprarenal aortic coarctation has resulted in long-term control of blood pressure and cardiac and renal function.
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PMID:Coarctation of the abdominal aorta. 852 35

Although hypothermia and cardioplegic cardiac arrest provide effective protection during cardiac surgery, ischemia of long duration, poor preoperative myocardial function, and ventricular hypertrophy may lead to heterogeneous delivery of cardioplegic solutions, incomplete protection, and impaired postischemic recovery. Calcium antagonists are potent cardioprotective agents, but their efficacy in the presence of cold cardioplegia is still controversial, especially in heart failure, since it is often believed that failing hearts are more sensitive to their negative inotropic and chronotropic actions. However, recent data have demonstrated that the benzothiazepine-like calcium antagonists diltiazem and clentiazem, in selected dose ranges, elicit significant cardioprotection independently of intrinsic cardiodepression, thus lending support to their use in cardioprotective maneuvers involving the failing heart. We therefore evaluated the cardioprotective interaction of diltiazem, clentiazem, and cold cardioplegia in both normal and failing ischemic hearts. Hearts were excised from 200- to 225-day-old cardiomyopathic hamsters (CMHs) of the UM-X7.1 line and age-matched normal healthy controls. Ex vivo perfusion was performed at a constant pressure (140 cmH2O; 1 cmH2O = 98.1 Pa) according to the method of Langendorff. Heart rate, left ventricular developed pressure (LVDP), and coronary flow were monitored throughout the study. Global ischemia was produced for 90 min by shutting down the perfusate flow, followed by reperfusion for 30 min. Normal and failing CMH hearts were either untreated (control) or perfused at the onset of global ischemia with one of the following combinations: cold cardioplegia alone (St. Thomas' Hospital cardioplegic solution, 4 degrees C, infused for 2 min), cold cardioplegia + 10 nM diltiazem, or cold cardioplegia + 10 nM clentiazem. The cardiac and coronary dilator properties of 10 nM diltiazem and 10 nM clentiazem alone were investigated in separate groups of isolated preparations. Failing CMH hearts had lower basal LVDP (42 +/- 2 vs. 77 +/- 2 mmHg (1 mmHg = 133.3 Pa) for normal hearts, p < 0.05), while coronary flow was only slightly reduced (5.6 +/- 0.2 vs. 6.2 +/- 0.2 mL/min for normal hearts). Following 90 min global ischemia, coronary flow was increased in both groups, but the peak hyperemic response declined only in failing CMH hearts (+50 +/- 17 vs. +82 +/- 17% in normal hearts). In normal hearts, LVDP virtually recovered within 5 min of reperfusion but steadily decreased thereafter (-37 +/- 4% at 30 min). In contrast, in failing CMH hearts, LVDP significantly decreased early during reperfusion but improved over time (-19 +/- 7% at 30 min). In normal hearts, the addition of diltiazem or clentiazem to cold cardioplegic solutions resulted in improved postischemic contractile function for the duration of reperfusion (85 +/- 4% vs. only 71 +/- 6% for cardioplegia, p < 0.05). The post-ischemic increase in coronary flow was similar in all groups. In failing CMH hearts, the addition of diltiazem or clentiazem afforded no significant contractile benefit at reperfusion. In nonischemic normal hearts, infusion of diltiazem or clentiazem (10 nM) alone increased coronary flow (+6 +/- 1% for diltiazem and +24 +/- 3% for clentiazem) without significant negative inotropic or chronotropic effects. In nonischemic failing CMH hearts, infusion of diltiazem or clentiazem did not elicit cardiodepression. In contrast their coronary dilator actions reverted to vasoconstriction (diltiazem) or were significantly attenuated (clentiazem). From these experiments we can conclude that, compared with the normal heart, the failing CMH heart adapted differently to global ischemia.
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PMID:Resistance of the failing dystrophic hamster heart to the cardioprotective effects of diltiazem and clentiazem: evidence of coronary vascular dysfunctions. 856 77


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