Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enhancement of ATP regeneration following global myocardial ischemia in dogs by both ATP catabolic enzyme blockade and precursor infusion was investigated. The breakdown of AMP to adenosine is catalyzed by 5'-nucleotidase and this enzyme was inhibited during the ischemic period with either concanavalin A (Con A, 3 mg/kg) or alpha, beta-methyleneadenosine 5'-diphosphate (AMP-CP, 250 microM). To provide additional ATP precursors, adenine (30 mg/kg) and ribose (25 mg/kg) (A/R) were also infused into the coronary vasculature during ischemia and recovery on cardiopulmonary bypass. Left ventricular myocardial ATP levels in control animals decreased to 52% of preischemic values during aortic cross clamping, but ATP levels in dogs treated with AMP-CP + A/R fell to only 67% of preischemic values (P less than 0.05). During reperfusion, ATP levels in Con A + A/R (3.43 +/- 0.26 mumol/g wet wt) and AMP-CP + A/R (3.77 +/- 0.42) treated animals were higher than values found in control dogs (2.73 +/- 0.16, P less than 0.05). Infusions of A/R alone without enzyme inhibition did not increase ATP regeneration. The adenine nucleotide energy charge ratio was also increased by enzyme blockade with either inhibitor when combined with precursor infusion. On bypass, left ventricular myocardial blood flow (measured by the microsphere technique) was increased by 140% (P less than 0.01) over control values in all groups receiving A/R; therefore, enhanced ATP levels were not merely the result of increased flow. Renal blood flow was not adversely affected by this combination of drugs as has been previously found with adenosine infusion and inhibition of adenosine catabolism.
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PMID:Prevention of ATP catabolism during myocardial ischemia: a preliminary report. 683 14

The studies concerned age-dependent peculiarities of the vasopressin effect on the hemodynamics and tone of the coronary vessels in dogs, the contraction of the isolated vascular strip in rats, and the hemodynamic and ECG indices in rabbits and in rats. The data obtained indicate the great sensitivity of old vessels to vasopressin. In aging, both humans and animals show a rise of vasopressin concentration in the blood. Age-dependent differences of the vasopressin effect on the kallikrein-kinin system, adenosine metabolism, the contents of prostaglandins and cyclic AMP have been established. High sensitivity to vasopressin in combination with its increased concentration in the blood is an important factor that contributes to the development of arterial hypertension and ischemic heart disease.
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PMID:Vasopressin and cardiovascular system in aging. 692 18

During the induction of myocardial infarction in the rat by isoproterenol, a decrease in the voltage of the T wave in the electrocardiogram is produced, which reflects myocardial ischemia through a previous infusion of a KCl solution; while the perfusion of NaCl increases the voltage of such wave and therefore cardiac ischemia. The values of free Pi in the myocardium increase significantly with the administration of isoproterenol. If KCl has been perfused previously, the figures of free Pi are superior in 155% of those obtained with the perfusion of NaCl. The values of all the energetic phosphates, AMP, ADP and ATP decrease inversely and in a significant way with isoproterenol and the perfusion of NaCl and KCl. The activity of creatine-phosphokinase in the myocardium decreases with isoproterenol, specially with the previous perfusion of KCl Similarly, the activity of the isoenzimes of lactic dehydrogenase L1 and L2 (alpha-HBDH), decreases, which intensifies with previous perfusion of NaCl, but diminishes with KCl. The activity of malicodehydrogenase (MDH) in the myocardium decreases with isoproterenol, even with the previous perfusion of NaCl, but in lesser degree than with KCl.
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PMID:[Effect of sodium and potassium on cardiac infarct in rats]. 721 55

Experimental alimentary hypercholesterolaemia in rabbits caused not only a decrease in deamination of monoamines (serotonin, benzylamine, tyramine) in liver, brain, kidney and heart mitochondrial fractions but also an appearance in these fractions of a qualitatively new reactions, namely that of cadaverine deamination, which was occasionally accompanied by stimulation of AMP deamination. In mitochondrial fractions from liver tissue obtained by autopsy in cases of ischemic heart disease accompanied by atherosclerosis, as compared with the corresponding fractions from the liver of persons who died in accidents and in whom no distinct morphological manifestations of atherosclerosis could be noted, there was observed a decrease in deamination of serotonin or tyramine (by 52% and 63%), appearance of cadaverine deamination (Vmax constitutes 35% of the Vmax value for serotonin deamination in the same fraction (and stimulation) 2-fold) of AMP deamination. The impairments in deamination of the nitrogenous compounds in experimental hypercholesterolaemia and in atherosclerosis are apparently due to qualitative alteration (transformation) in catalytic properties of mitochondrial monoamine oxidases. Implications of this hypothesis for future research on treatment of atherosclerosis are discussed.
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PMID:[Mechanism of disturbances in the deamination of nitrogenous compounds in experimental hypercholesterolemia and atherosclerosis]. 733 59

Use of non-selective beta-blockers: Non-selective beta-blockers reduce blood pressure by reducing cardiac output. They have a proven record of efficacy, alone or in combination with other drug classes, in the treatment of hypertension, ischemic heart disease and some tachyarrhythmias. They have also proved effective in the primary and secondary prevention of myocardial infarction. However, adverse effects include increased peripheral resistance, limitation of exercise tolerance, and bradyarrhythmia, cold extremities and bronchoconstriction in susceptible patients. Effects of beta 1-selective blockers: beta 1-Selective antagonists cause less vasoconstriction and less bronchoconstriction than non-selective beta-blockers, but the reduction in cardiac output may still activate a sympathetically mediated increase in peripheral resistance. beta 1-blockers with beta 2 agonist activity are vasodilatory because they activate postsynaptic beta 2 receptors on vascular smooth muscle cell membranes, via the formation of cyclic AMP. Non-selective beta-blockers with alpha 2-adrenoceptor blocking activity: Non-selective beta-adrenoceptor blockers with alpha 1-adrenoceptor blocking activity, such as carvedilol, labetalol, medroxalol and bucindolol, combine the advantages of beta- and alpha 1-blockade, including peripheral vasodilation. As an example of this class of agent, carvedilol has been shown to be effective in the treatment of hypertension by reducing peripheral resistance. There are some indications, still to be confirmed, that it improves left ventricular diastolic function and causes regression of left ventricular hypertrophy, and that it may be useful in the treatment of some patients with congestive heart failure or arrhythmia. In animal models of myocardial ischemia, carvedilol has proved to be cardioprotective.
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PMID:Beta-blocking agents with vasodilator activity. 810 40

OPC-18790 is a positive inotropic and vasodilating agent that increases intracellular cyclic AMP and stimulates Ca currents. We examined its direct electrophysiological effects in isolated blood-perfused canine cardiac preparations. OPC-18790 caused an acceleration of the intraventricular conduction in association with an increase of the contractile force and the coronary blood flow. We also examined the effects of OPC-18790 on ventricular arrhythmias in canine ventricular tachycardia (VT) models. OPC-18790 in doses producing submaximal inotropic effects, 3 mg/kg, i.v., increased the total heart rate, atrial rate and decreased the blood pressure, but did not suppress or aggravate 24- and 48-hr coronary ligation VTs. OPC-18790 up to 3 mg/kg, i.v. also did not suppress or aggravate digitalis-induced VTs. However, this dose of OPC-18790 aggravated halothane-adrenaline induced VT into ventricular fibrillation and eventually death, but a lower dose of 0.3 mg/kg did not aggravate this VT. These results in canine VTs indicate that OPC-18790 is similar to other positive inotropic agents, vesnarinone, amrinone, milrinone and sulmazole. The absence of an aggravating effect of this new positive inotropic agent on digitalis and coronary ligation VTs may be advantageous in a clinical setting of combined therapy with digitalis for myocardial ischemia.
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PMID:Effects of OPC-18790, a new positive inotropic agent, on canine ventricular arrhythmias. 810 32

The common underlying heart diseases were ischemic heart disease (39%), valvular heart disease (27%), hypertensive heart disease (10%) in 104 patients (mean age 79 yrs) with congestive heart failure (CHF). Cardiomyopathy (5%) and congenital heart disease (2%) such as atrial septal defect were less common. In addition, many extracardiac diseases including anemia, hypothyroidism, renal failure and pulmonary disease contributed to the etiology of CHF in the elderly. Cardiac amyloidosis should be considered as an uncommon cause of refractory CHF. While the precipitating factor was not found in half of the 104 patients with CHF, the most common factors were respiratory infection, myocardial ischemia and arrhythmia. In addition, inappropriate drug usage including poor drug compliance, the use of beta-blockers and excessive intake of sodium and fluid precipitated or exacerbated heart failure. Renal failure was a most important complication and predisposed to refractory CHF. Aged patients with mild CHF (NYHA class II) showed an insufficient production of cyclic AMP and GMP in proportion to the increases of norepinephrine and atrial natriuretic peptide in comparison with health aged subjects after the submaximal treadmill exercise test. This finding may suggest that an inadequate compensation of neurohumoral factors is prone to cause CHF in the elderly. Appropriate management of acute CHF in the elderly begins with recognition of the underlying heart disease, complications and the severity of cardiac function. In addition to medical management including loop diuretics, vasodilator, beta-receptor agonist and phosphodiesterase inhibitor, cases associated with respiratory and renal failure require mechanical ventilation and continuous hemofiltration.
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PMID:[The etiology and management of congestive heart failure in the elderly]. 820 67

The effect of 5'-nucleotidase inhibitor (AMP-C) and xanthine oxidase inhibitor (Allopurinol: ALLO) on myocardial functional recovery and the restoration of myocardial high energy phosphates after 15 min of normothermic global ischemic insult, was studied in the isolated isovolemic Langendorff rat heart model. Fifty nine rats were divided into 4 groups: Group I; saline, Group II; AMP-C plus ALLO, Group III; AMP-C, Group IV; ALLO. Intermittent infusion of drugs was delivered in 3 ml of solution at 5 min intervals during ischemia. Percent recovery of left ventricular systolic function was as follows: Group I; 74.2 +/- 3.6%, Group II; 87.7 +/- 1.7%, Group III; 83.5 +/- 3.1%, Group IV; 86.4 +/- 2.6%. Improved recovery was statistically significant only in Group II (p < 0.05 vs Group I). Suppression of reactive hyperemia was seen with reperfusion in the groups which had been treated with AMP-C (i.e., Groups II and III). Myocardial adenine nucleotides and purines were measured in 6 hearts in each group using high performance liquid chromatography. Myocardial ATP levels was 0.89 +/- 0.16 nmol/mg left ventricular wet weight in Group I, 1.37 +/- 0.12 in Group II (p < 0.05 vs Group I), 1.42 +/- 0.17 in Group III (p < 0.05) and 1.17 +/- 0.15 in Group IV. This study demonstrates that intermittent infusion of AMP-C plus ALLO during global myocardial ischemia results in improved myocardial functional recovery and improved preservation of high energy phosphates.
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PMID:Evaluation of the effectiveness of 5'-nucleotidase inhibitor and allopurinol in myocardial ischemia. 835 99

The mechanism by which thromboxane A2 (TXA2) causes its detrimental actions on the myocardium during ischemia and reperfusion injury is unknown. The present study was designed to investigate the influence of U46619, a stable TXA2 analog, on intracellular Ca transients in electrically stimulated single neonatal rat ventricular myocytes by using spectrofluorometric analysis of fura-2-Ca binding. Administration of U46619 increased basal and peak Ca concentrations as well as width of electrically induced Ca transients in a concentration-dependent manner (0.1-1 microM) during a 1-hr exposure. Exposure to 10 microM U46619 caused irregular Ca transients and a marked increase in cytosolic-free Ca concentration. The effects of U46619 were antagonized by the TXA2 receptor antagonist SK&F95585 (2 microM), dibutyryl cyclic AMP (1 mM), verapamil (1 microM) and ryanodine (1 microM). U46619 did not affect the increase in cytosolic Ca induced by KCl (90 mM) depolarization. Caffeine (10 mM)-induced Ca release from the sarcoplasmic reticulum was enhanced markedly in U46619-treated cells. Significant lactate dehydrogenase leakage from the myocytes did not occur at 1 to 10 microM U46619. These results indicate that the increase in Ca transients by U46619 is a receptor-mediated process leading to a Ca accumulation in the sarcoplasmic reticulum which is likely to be responsible for an enhanced cytosolic Ca during excitation-contraction coupling. Thus, the identification of U46619-induced alterations of Ca dynamics appears to provide, at the cellular level, a direct role for TXA2 during myocardial ischemia and reperfusion.
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PMID:Alterations by a thromboxane A2 analog (U46619) of calcium dynamics in isolated rat cardiomyocytes. 842 35

Platelet activation by the stable endoperoxide analogue U46619 is mediated largely by ADP released from platelet-dense granules. Polymorphonuclear leukocytes (PMNs) endowed with ecto-ADPase activity may operate as antiaggregatory cells in platelet aggregation induced by U46619. Unstimulated PMNs were effective in reducing aggregation when platelets were stimulated by threshold concentrations of U46619, whereas at higher concentrations of the stimulus, PMN activation is required. Evidence that the inhibition was mediated by PMN ecto-ADPase activity was obtained by high-performance liquid chromatography analysis, indicating that PMNs were able to efficiently metabolize platelet-active ADP into AMP. Moreover, PMN-derived supernatants were able to inhibit platelet aggregation, suggesting that under this circumstance the inhibition was exerted by an uncharacterized, releasable ADPase activity. This study supports the hypothesis that, besides nitric oxide and hydrogen peroxide, ADPase activity may represent another PMN-mediated pathway capable of regulating platelet activity in areas of reduced blood flow, such as those found in conditions of myocardial ischemia.
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PMID:Platelet aggregation induced by the endoperoxide analogue U46619 is inhibited by polymorphonuclear leukocyte ADPase activity. 848 21


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