ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Previously, we demonstrated that there were effects of elevated plasma osmolality on both early cell swelling and eventual cell necrosis in ischemic cardiac muscle. The present study quantifies the extent of cell volume derangement, determines whether or not there is a quantitative relationship between cell swelling and eventual necrosis, and defines the time limits of ischemia within which prevention of early swelling by hyperosmotic intervention can reduce eventual necrosis. Com-puter-assisted analysis of tissue pathology was used for quantification of myocardial cell swelling early during ischemia. The results then were correlated with the extent of eventual necrosis. When canine posterior papillary muscle was sampled for electron microscopy soon after the restoration of blood flow following proximal circumflex artery occlusion, stereological methods revealed a substantial increase in myocardial cell volume. The data define the spectrum of volume gain in ischemic myocardial cells. The effectiveness of an osmotic intervention with mannitol in preventing cell swelling and eventual necrosis was limited to ischemic periods of less than 90 minutes. There was a strong linear correlation between the fractions of cells with increased volume (whether the increase was measured as cytoplasmic space, mitochondrial volume, or overall volume expansion), and the fraction of cells necrotic 12 hours after restoration of blood flow. The pattern of action of osmotic intervention in the prevention of ischemic cell swelling and in diminishing eventual necrosis in this model suggests strongly that there is an important relationship between a failure in cell volume regulation and eventual cell death in myocardial ischemia.Circ Res 47: 653-665, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We studied the effects of the local anesthetics, procaine and benzocaine, on the action potential and force of canine ventricular muscle and Purkinje fibers. In ventricular muscle, procaine often shifted the plateau to a more positive value and increased the force of contraction, whereas benzocaine shortened the action potential and decreased contractile force. In Purkinje fibers, both local anesthetics reduced contractile force and decreased the duration of the action potential markedly. In ventricular muscle fibers norepinephrine potentiated the positive inotropic effect of procaine and changed the effects of benzocaine from a negative to a positive inotropic effect. The potentiating effect of procaine on contraction was eliminated by propranolol. In the presence of norepinephrine (and the absence of propranolol), in Purkinje fibers both anesthetics decreased force but less than in the absence of norepinephrine. In the presence of tetrodotoxin (TTX) and norepinephrine, procaine and benzocaine increased contractile force of muscle fibers. Under the same conditions in Purkinje fibers, procaine increased contractile force and benzocaine decreased it (but less than in the absence of TTX). Admin-istration of veratridine increased contractile force in both ventricular muscle and Purkinje fibers: under these conditions, both local anesthetics decreased contractile force in both tissues. We conclude that: (1) the positive inotropic effects of procaine and benzocaine are mediated through an adrenergic mechanism; (2) the negative inotropic effect is at least in part mediated through a reduction of sodium influx; and (3) the negative inotropic effect is more pronounced in Purkinje fibers because of a larger steady state sodium influx during the plateau.Circ Res 47: 666-674, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

The effects of sodium, sympathetic innervation, and central adrenergic structures on the development of changes in renal vascular reactivity were studied in unilaterally nephrectomized rats treated with a single implant of deoxycorticosterone acetate (DOCA; 100 mg/kg). Vascular reactivity to norepinephrine (NE) and vasopressin (ADH) was assessed in isolated kidneys perfused with a synthetic medium. Influence of sodium was determined by placing DOCA-treated rats on high, normal, and low sodium intakes. Neural influence was studied by means of local denervation of the renal artery and by intravenous (iv) and intraventricular (ivt) administration of 6-hydroxydopamine (6-OHDA). Marked changes in renal vascular reactivity in DOCA-treated rats were already apparent prior to the rise in blood pressure. Dose-response curves for NE and ADH showed parallel leftward shifts and decreased threshold doses. Normal sodium intake, local denervation, and peripheral sympathectomy had no effect on the development of these vascular changes in DOCA-treated rats. However, sodium deficiency and ivt administration of 6-OHDA totally prevented development of enhanced vascular reactivity. These results imply that increased vascular reactivity is a major factor in the development of DOCA-hypertension.Circ Res 47: 675-683, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Adenosine and related compounds can produce atrioventricular (A-V) conduction block. Similar conduction disturbances are observed in myocardial hypoxia. To investigate the possibility that adenosine might be causally involved in hypoxic conduction disturbances, we measured A-V conduction times, subdivided into atrial-to-His bundle (A-H) and His bundle-to-ventricular (H-V) intervals, with extracellular electrodes in isolated rabbit and guinea pig hearts perfused with modified Krebs-Henseleit solution. Adenosine produced dose-dependent prolongation of A-V conduction time in both species, although guinea pig hearts responded to lower doses (10−7M) and showed a steeper dose-response relationship than rabbit hearts. Higher adenosine doses produced second-degree heart block in both species. Conduction delay was confined to the A-H interval, implicating action on A-V node cells. Further investigation of guinea pig hearts revealed a specific antagonism towards adenosine's effects by 10−5M aminophylline. Conduction disturbances produced by acetylcholine or MnCl2were unaffected by aminophyline as were adenosine's effects by atropine. Perfusion with hypoxic perfusate caused A-V conduction delays and second-degree block in guinea pigs hearts. This effect was dramat-ically attenuated by aminophylline. We conclude that endogenously released adenosine may cause at least some of the A-V conduction disturbances associated with acute myocardial hypoxia. Furthermore, methylxanthines may prove to be of therapeutic value in combatting such disturbances in a clinical setting.Circ Res 47: 684-691, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

K+-and Na+-selective liquid ion-exchanger microelectrodes were used to measure intra-cellular K+activity (ak) and intracellular Na+activity (alj.) of sheep cardiac Purkinje strands in different solutions. In Tyrode's solution with an extracellular K+concentration ([K+]o) of 5.4 mM, ak was between 80 and 140 mM and averaged 109.6 ± 4.0 mM (mean ± SE, 20 strands). The measured ak was closely correlated with the resting membrane potential, so that the K+equilibrium potential was always about 10 mV more negative. When [K+]owas lower than 5.4 mM, ak fell, and when [K+]owas higher than 5.4 mM it increased, ajj. was between 4 and 12 mM, and averaged 6.6 ± 0.6 mM (14 strands). Its variation was also correlated with resting potential. Over a wide range of [K+]oand extracellular Na+concentrations ([Na*],), the af,achanges were such that Na* equilibrium potential remained between +70 and +80 mV. The quiescent membrane behaved as a K+-electrode when fK+lowas higher than 5.4 mM. When [K+]owas low and [Na+]owas zero, then Ca2+and perhaps Cl— contributed to the resting potential.Circ Res 47: 692-700, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

The present study assesses effects of acutely infarcted myocardium on apparent micro-sphere loss as a function of time, determines effects of apparent microsphere loss on blood flow measurements to ischemic regions, and determines to what extent apparent microsphere loss alters interpretation of serial measurements of collateral blood flow. Studies were performed in 35 awake mongrel dogs chronically instrumented with catheters in the aorta and left atrium and an occluder on the proximal circumflex coronary artery. Myocardial blood flow was measured before and 15 minutes after complete occlusion. Dogs were randomly divided into four groups to be killed at 6 and 24 hours, and 3 and 6 days. In the 3-day group, an additional blood flow measurement was made 24 hours postocclusion. The entire left ventricle was sectioned into 1– to 2-g samples and myocardial blood flow determined. The ratio of preocclusion blood flow in each ischemic sample to mean nonischemic flow was used to calculate apparent microsphere loss and to correct ischemic blood flow in each sample. Significant apparent microsphere loss occurred in epicardial layers at 24 hours and in epi-and endocardial layers at 3 and 6 days; maximum loss at each interval was 22.3,19.4, and 22.2% respectively. Absolute blood flow corrections for ischemic myocardium were small, range —0.035 to 0.083 ml/min per g. Changes in flow to ischemic regions between 15 minutes and 24 hours were comparable before and after correction for apparent microsphere loss. Although infarction resulted in significant apparent microsphere loss, effects on ischemic blood flow measurements were very small and consequently did not prevent interpretation of serial blood flow measurements after infarction in animals killed at 3 days.Circ Res 47: 701-709, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Some evidence indicates that the inotropic effect of cardiac glycosides occurs at concen-trations too low to affect Na+,K+ATPase activity. This suggests that some receptor other than Na -ATPase mediates the inotropic effect. We studied ouabain binding to sarcolemma-enriched prepara-tions from canine ventricle under conditions known to promote binding to Na+,K+-ATPase. Profiles for binding and dissociation were characterized by two kinetic components: (1) fast association and slow dissociation; (2) slow association and fast dissociation. Profiles in the absence of supporting ligands were consistent with a single species of receptors with slow association, fast dissociation and minimal effect on Na+,K+-ATPase activity. Binding supported by magnesium plus inorganic phosphate inhibited Na+,K-ATPase activity by 86%. The two binding components were affected differentially by heating at 55°C. It was concluded that the preparation possesses two receptors for ouabain: the Na +,K-ATPase and a "new" receptor. The latter may be different chemically from the Na +,K-ATPase. The more likely possibility is that the "new" receptor is the Na +,K-ATPase in a state characterized by low catalytic activity, low affinity for ouabain, and no requirement of specific ligands for ouabain binding. Further, the data suggest an interdependence between the two forms. This leads to a mechanism which allows an inotropic effect to precede loss of Na +,K-ATPase activity even though both result from glycoside binding to Na,K-ATPase. The mechanism involves an equilibrium between inactive and active forms of the Na +,K-ATPase such that the inactive form buffers loss of the active form upon exposure to a cardiac glycoside.Circ Res47: 710-720, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

The amount of readily exchangeable Ca2+in mitochondria of an isolated working rat heart is less than 10 ng-ions/g heart. We therefore conclude that either no Ca2+enters mitochondria or that the Ca2+which does enter is removed continuously. Using Sr2+and Mn2+we obtained evidence that the mitochondrial Na+-Ca2+exchanger was indeed operational in releasing metal from mitochon-dria of the heart. When Ca2+in the perfusate was replaced by Sr2*, we found that a significant amount of Sr2+(approximately 100 ng-ions/g heart) entered mitochondria. When the heart then was returned to a Ca2+-containing perfusate, over 80% of the Sr2+was washed out of mitochondria within 30 seconds. When low levels of Mn2+were added to the perfusate, we found that Mn accumulated in mitochondria irreversibly. This is evidence for the operation of the Na +-Ca2+exchanger because Na was found to release Ca2+and Sr2+but not Mn from isolated rat heart mitochondria. Our estimates indicate that when the Na +-Ca2+exchanger is maximally operative, as in the Sr^-perfused heart, the flux of Sr2+through mitochondria is at most 10% of the total flux needed for the activation of contraction. The low level of Ca2+in the mitochondria of Ca -perfused hearts suggests a much smaller flux of through the mitochondria in this case. We therefore conclude that mitochondria play little if any role in the beat-to-beat regulation of normal Ca2+fluxes in the rat heart.Circ Res 47: 721-727, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

An isotropic, initially spherical, membrane model of the infarcted ventricle satisfactorily predicts ventricular function in the infarcted heart when compared to clinical information and available ventricular models of higher complexity. Computations based on finite element solutions of this membrane model yield end-diastolic and end-systolic pressure-volume curves, from which ventricular function curves are calculated, for infarcts of varying size and material properties. These computations indicate a progressive degradation of cardiac performance with increasing infarct size such that normal cardiac outputs can be maintained with Frank-Starling compensation and increased heart rate for acute infarcts no larger than 41% of the ventricular surface. The relationship between infarct stiffness and cardiac function is found to be complex and dependent on both infarct size and end-diastolic pressure, although moderately stiff subacute infarcts are associated with better function than extensible acute infarcts. Also, calculations of extensions and stresses suggest considerable disruption of the border zone contraction pattern, as well as elevated border zone systolic stresses.Circ Res 47: 728-741, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID