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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The energy production (heat + work) of cardiac muscle must be interpreted in terms of the major ATPases underwriting cardiac contraction; these are the Ca2+ and Na+-K+ transport ATPases and actomyosin ATPase. It is possible to apply the classical phenomenological subdivisions to cardiac energy production; when this is done, certain properties immediately distinguish cardiac muscle from skeletal muscle. Little or no temporal distinction exists between initial (anaerobic) and recovery (oxidative) metabolism. Even at temperatures as low as 20 degrees C most of the recovery heat is released within the time course of a single contraction. Cardiac muscle is characterized by a high resting heat rate, the magnitude of which varies between species and depends on the metabolic substrate. In isometric contractions there is a slightly curvilinear relationship between developed force and heat production. There is a tension-independent or activation component, the magnitude of which reflects the prevailing level of contractility and is probably associated with calcium release and retrieval. In isotonic contractions energy production is maximal when the muscle is heavily loaded but falls steeply when the size of the load is reduced. The enthalpy:load relation is probably similar to that found in twitch contractions of skeletal muscle working at room temperature or above; but, unlike for skeletal muscle, there are families of such curves: At any instant of time the relation depends upon the prevailing physiological conditions (e.g. stimulus rate, substrate supply, humoral agents, extracellular ionic concentrations, initial length). Cardiac energy production can be estimated by a variety of other techniques (such as high-energy phosphate utilization, oxygen consumption, and changes in tissue fluorescence related to pyridine nucleotide oxidation levels). At the present time there is considerable agreement between heat measurements and results obtained with these different techniques. We should like to conclude on a cautionary note. First, there is considerable variability in the properties of cardiac muscle from different species. Significant variations occur at nearly all levels of cellular function--e.g. shape of action potential, electrical and mechanical dependence upon stimulus history, mechanisms of excitation-contraction coupling, actomyosin ATPase activity, metabolic regulation, and differential sensitivity to anoxia or ischemia. Second, the types of contractions readily studied in isolated papillary muscles (i.e. isometric or isotonic twitches) may not necessarily be the best mechanical paradigms for understanding myocardial energetics in vivo. The particular geometric demands of individual research techniques require the use of a wide variety of myocardial preparations from a wide variety of species. This necessarily produces a pastiche view of cardiac muscle rather than an integrated picture of some hypothetically typical mammalian myocardium.
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PMID:Cardiac heat production. 21 64

Myoglobin is the oxygen-binding protein characteristic of skeletal and cardiac muscle. With muscle disease or dysfunction, myoglobin may enter the circulation, and after renal clearance, it may also appear in the urine. Therefore, the presence of myoglobinemia and myoglobinuria may serve as indicators of the presence and severity of muscle disease. With newly developed methods of detection, myoglobinemia and myoglobinuria are now recognized as complications of trauma, ischemia, surgery, states of exertion and stress, metabolic abnormalities, inherited enzyme disorders, toxin and drug actions, and inflammatory states. Infarction of the heart muscle also can be detected by myoglobin assay. Persistent myoglobinuric states may be complicated by renal failure and electrolyte imbalance. The diagnosis of myoglobinemia and myoglobinuria can be now confirmed with the use of immunoassay techniques. Although not yet widely available, they offer the possibility of the specificity and sensitivity needed for clinical use.
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PMID:Myoglobin: methods and diagnostic uses. 40 72

Myocardial relaxation is an important energy-dependent process. Hypoxia, unlike ischemia, has not been shown to impair myocardial relaxation. This difference may be because (a) the traditional index to assess isometric muscle relaxation (half time to relaxation or RT((1/2))) reflects both changes in developed tension as well as relaxation and (b) the relaxation process is highly sensitive to temperature and previous papillary muscle studies have been conducted under hypothermic conditions. The present study examines the effect of hypoxia on the relaxation process of 31 isometrically contracting kitten papillary muscles at hypothermic (29 degrees C) and euthermic (38 degrees C) conditions using RT((1/2)), the peak rate of tension fall (-dT/dt) and -dT/dt normalized for tension ([peak -dT/dt]/T and max [-dT/dt per T]). Hypoxia at 29 degrees C resulted in a fall in RT((1/2)) from 278+/-11 (SEM) to 230+/-17 ms (P < 0.01) and no change in (peak -dT/dt)/T and max (-dT/dt per T). However, at 38 degrees C, hypoxia impaired relaxation as reflected in a prolongation of RT((1/2)) from 101+/-6 to 126+/-8 ms (P < 0.01) in spite of a substantial fall in peak tension. Moreover, (peak -dT/dt)/T decreased from -15.4+/-0.7 to -11.0+/-0.8/s (P < 0.01) and max (-dT/dt per T) decreased from -25.1+/-1.8 to -13.8+/-0.9/s (P < 0.01). In conclusion, the present study demonstrates that hypoxia impairs the relaxation process of cardiac muscle.
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PMID:Effect of hypoxia on myocardial relaxation in isometric cat papillary muscle. 65 89

The effects of lidocaine infusion on the ultrastructural damage induced in cardiac muscle by normothermic cardiopulmonary bypass were assessed in 15 dogs. Six dogs received no medication other than sodium pentobarbital (25 mg/kg, intravenously) while 9 dogs were treated with lidocaine after anesthesia. Lidocaine was given as a 2-mg/kg loading dose 10 minutes prior to ischemic arrest and a 2-mg/min continuous infusion during the entire experimental period. Biopsy samples of the left ventricular apex were taken 15 and 45 minutes after the start of ischemic arrest and 5 minutes after resumption of coronary blood flow. Biopsy samples were also obtained from 4 animals after thoracotomy to serve as controls for experimental procedures. Myocardial ultrastructure in the 4 control animals was comparable to that reported by other investigators. Five of 6 of the nontreated dogs and 8 of 9 lidocaine-treated dogs survived the entire period of ischemia and 5 minutes of coronary reperfusion. However, the extent of ultrastructural damage varied considerably between the two groups. In the experimental dogs receiving no lidocaine, mitochondria were swollen, cristae were absent, the mitochondrial matrix was cleared, and sarcomeres were disrupted. Myelin figures and contraction bands were also observed. None of the surviving lidocaine-treated animals had ultrastructural changes comparable to the worst ones in nontreated dogs. Damage was limited to some swelling of mitochondria with focal clearing of matrix. Most cristae remained intact. There were no myelin figures and few contraction bands. The results suggest that lidocaine protects the integrity of ischemic myocardium. It is suggested that this protection resulted from stabilization of plasma and/or mitochondrial membranes. (Am J Pathol 87:399-414, 1977).
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PMID:Reduction of ischemic myocardial damage in the dog by lidocaine infusion. 85 Nov 72

It has been proposed that taurine, or one of its metabolites, may exert anti-arrhythmic effects in cardiac muscle. The present studies examined the effects of acute left ventricular ischemia in the dog (in vivo) and whole heart anoxia in the perfused rat heart (in vitro) on the content and distribution of taurine. In control dogs an increasing outer-to-inner gradient in taurine content was observed in the left ventricle. Left circumflex artery ligation for four hours markedly decreased tissue taurine content, the greatest disappearance occurring in the inner zone. Anoxic perfusion resulted in a similar decrease in rat ventricular taurine levels. Recovery of taurine in the heart perfusates indicated that tissue disappearance, secondary to oxygen deficiency, involved leakage into the extracellular fluid rather than metabolic conversion.
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PMID:Cardiac muscle taurine: effects of acute left ventricular ischemia in the dog and anoxic perfusion of the rat heart. 103 80

Coronary artery ligation with or without reperfusion was carried out in Wistar rats to study the role of coronary microcirculatory factors and membrane permeability alteration of cardiac muscle cell in the evolution of cardiac muscle cell injury by using the fine structural extracellular protein tracer, horseradish peroxidase (HRP). The findings were compared with those obtained in noncoronarogenic myocardial injury models following administration of norepinephrine, a pressor, and isoproterenol, a depressor catecholamine. Following left coronary artery ligation lastingfor 10 and 20 minutes, some of the collaterals in the ischemic zone were perused by the tracer, but the numer of patent capillaries decreased during 60-min ligation. The inhomogeneous involvement of cardiac muscle cells in ischemic injury correlated well with these microcirculatory findings. In comparison to permanent ischemia, an abrupt deterioration of the cardiac muscle cell alteration occured after reperfusion with influx of HRP into the damaged cells. The binding of tracer to myofilaments was, however, a later event as compared to that seen in the catecholamine models. The latter observation implies that, in addition to microcirculatory factors, direct cardiac muscle cell stimulation should also be considered in the evolution of noncoronarogenic myocardial injury.
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PMID:Coronary microcirculatory factors and cardiac muscle cell injury. 103 11

Fibroblast growth factors (FGF) and type beta-1 transforming growth factor (TGF beta 1) are pleiotropic regulatory peptides which are expressed in myocardium in a precise developmental and spatial program and are up-regulated, in the adult heart, by ischemia or a hemodynamic burden. The accumulation of trophic factors after aortic banding supports the hypothesis that autocrine or paracrine pathways might function to mediate, in part, the consequences of mechanical load. Our laboratory has demonstrated that cardiac muscle cells are targets for the action of peptide growth factors and, more specifically, that modulation of the cardiac phenotype by basic FGF (bFGF) and TGF beta 1 strongly resembles the induction of fetal cardiac genes--including skeletal alpha-actin (SkA), beta-myosin heavy chain, and atrial natriuretic factor--which are characteristic of pressure-overload hypertrophy. Unexpectedly, and despite effects like those of bFGF on five other cardiac genes, acidic FGF (aFGF) was found to repress, rather than stimulate, SkA transcription in neonatal cardiac muscle cells. The proximal 200 nucleotides of a heterologous SkA promoter were sufficient for basal tissue-specific transcription, for induction by bFGF, and for inhibition by aFGF. Thus, both positive and negative regulation by peptide growth factors can be localized to the proximal SkA promoter. Full promoter activity required each of three CC[A/T]6GG motifs similar to the serum response element (SRE) for activation of the c-fos proto-oncogene, as previously shown for SkA transcription in a skeletal muscle background. The most proximal SRE, SRE1, was sufficient in the absence of other SkA promoter sequences for efficient tissue-specific expression in cardiac myocytes (versus cardiac fibroblasts), and was stimulated by bFGF to the same extent as the full-length promoter and endogenous gene. Despite its ability to repress the SkA promoter, aFGF had no significant effect on SRE1. Both FGFs up-regulated the canonical fos SRE, to a comparable degree. Thus, SRE1 can discriminate between signals generated in cardiac myocytes by bFGF and aFGF. In cardiac myocyte extracts, two predominant proteins contact SRE1: serum response factor (SRF) and a second protein, F-ACT-1. Thus, serum response factor and F-ACT-1 are candidate trans-acting factors for basal transcription of the SkA gene in cardiac muscle cells and for induction of SkA by bFGF and, potentially, other trophic signals.
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PMID:Growth factors, growth factor response elements, and the cardiac phenotype. 128 69

Bepridil is an antianginal agent with multiple therapeutic actions. It decreases calcium influx through potential-dependent and receptor-operated sarcolemmic calcium channels and acts intracellularly as a calmodulin antagonist and calcium sensitizer. Thus, in cardiac muscle it enhances the sensitivity of troponin C to calcium, stimulates myofibrillar adenosine triphosphatase activity, removes calmodulin's inhibitory effect on sarcoplasmic reticulum calcium release, and inhibits sodium-calcium exchange--actions that tend to offset the effects of calcium influx blockade on cardiac contractile force. However, in vascular smooth muscle where the calcium-calmodulin complex promotes muscle contraction by activating myosin light-chain kinase phosphorylation of contractile proteins, calmodulin antagonism, coupled with bepridil's blockade of calcium influx, leads to vasorelaxation. In animal models of ischemia, bepridil and other calmodulin inhibitors show antiarrhythmic efficacy following reperfusion. Additionally, interfering with calmodulin's role in sympathetic nerve terminal function may help to limit the ischemia-induced catecholamine release that contributes to arrhythmogenesis. Bepridil shows a lidocaine-like fast kinetic block of inward sodium current (as distinct from the slow or intermediate kinetic inhibition expressed by encainide or quinidine, respectively). This inhibition is pH-dependent; activity is expressed to a greater degree at lower pH levels. This, this potentially antiarrhythmic mechanism is activated by conditions of ischemia. Bepridil's blockade of outward potassium currents and its inhibition of sodium-calcium exchange increase action potential duration and ventricular refractoriness, prolong the QT interval, and form the basis for a class III antiarrhythmic mechanism. Because hypokalemia also prolongs the QT interval, the addition of bepridil in the presence of hypokalemia can lead to excessive prolongation. Bepridil both increases myocardial oxygen supply through coronary vasodilation and decreases myocardial oxygen demand through mild heart rate and afterload reduction, and shows potential antiarrhythmic activity through class IB, III, and IV mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacology of bepridil. 137 85

The effects of plain ischemia (34 degrees C) and the protective role of hypothermia (20 degrees C) alone or in combination with cardioplegia (St Thomas' Hospital [STH] or glucose-potassium-nifedipine [GPN]) on the intracellular kinetics of the activator calcium of cardiac muscle were quantified and compared from the interval-force behaviour (mechanical restitution) of right and left ventricles of the perfused rat heart. Plain ischemia caused a major depression in the restitution of force of contraction of both ventricles, deranged the mixed linear-exponential functions by significantly increasing the time constants of the fitted mechanical restitution curves (MRC) and altered the control right/left ventricle interval-force relationship. The right ventricle was found to be more susceptible to ischemic damage than the left ventricle, and its inotropic reserve was virtually abolished by 1 h of plain ischemia. Hypothermic preservation during ischemia improved the mechanical restitution, salvaged the inotropic reserve and optimized right/left ventricle interval-force relationship, but the time constants of the fitted MRCs were still prolonged. However, both the cardioplegic formulations were equally effective in normalizing the time constants of the fitted curves. In general, right ventricle functions were better preserved by STH cardioplegia and left ventricle functions were better preserved by GPN cardioplegia. Cardioplegic interventions did not further improve the ventricular inotropic reserve compared with hypothermic preservation. Additional beneficial effects of cardioplegic formulations were directed towards stabilizing the linear-exponential functions and hence restitution of force of contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracellular kinetics of the activator calcium of rat heart after ischemic arrest and cardioplegia: quantitative comparison of right and left ventricles. 137 92

Pinacidil is a member of the new antihypertensive drug family possessing an action that involves an increased potassium efflux in vascular and cardiac muscle. We investigated the contribution of opening of ATP-sensitive potassium channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na+, K+, Ca2+, and Mg2+ in isolated rat hearts. After 30 min of normothermic global ischemia, pinacidil with 1 to 60 mumol/l failed to reduce the incidence of reperfusion-induced arrhythmias, even on the postischemic/reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (the duration of ischemia was reduced to 25 min), pinacidil treatment was associated with a greater incidence of reperfusion-induced arrhythmias (100%) as compared to the control value (50%). These proarrhythmic effects of pinacidil were also reflected in a maldistribution of myocardial ion contents both in nonischemic and ischemic/reperfused hearts. Cicletanine, a furopyridine antihypertensive agent that has no effect on coronary resistance, reduced the incidence of reperfusion arrhythmias, and its antiarrhythmic effect was antagonized by pinacidil. The same observation was made in relation to myocardial ion content, e.g., pinacidil-induced K+ loss and Ca2+ gain were antagonized by cicletanine, both in nonischemic and ischemic/reperfused hearts. It is hypothesized that the increased tendency to develop reperfusion-induced ventricular fibrillation is associated with the pinacidil-induced K+ efflux. The present study does not attempt to address the question of specific ionic currents; however, it has been suggested that proarrhythmic and antiarrhythmic effects of pinacidil and cicletanine, respectively, may relate to same receptor sites in which the latter may reflect a specific blockade of the outward K+ ion current via ATP-sensitive K+ channels. If this is so, the use of K+ channel openers as antihypertensive agents may be of particular concern in that population of postinfarction patients who are known to be at high risk of sudden coronary death.
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PMID:Reperfusion-induced arrhythmias and myocardial ion shifts: a pharmacologic interaction between pinacidil and cicletanine in isolated rat hearts. 141 6


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