摘要:

We think that the available data on adenosine formation suggest the two signals are responsible for adenosine release from cardiac myocytes: (1) the ratio of oxygen supply to demand and (2) agonisttriggered release of extracellular adenine nucleotides. We do not believe that the available data support the oxygen consumption hypothesis. The few studies which allow us to judge the relative importance of these two signals suggest that both hypoxia and sympathetic nerve stimulation release adenosine primarily by decreasing O2supply: demand. Agonist triggered nucleotide release may be quantitatively important in situations in which decreased O2supply/demand cannot explain increased release, i.e., isoproterenol and acetylcholine administration.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

After healing of experimental myocardial infarction in cat hearts, endocardial cells demonstrate persistent regional electrical changes. These include long action potential duration in surviving cells over the infarct scar, and short action potential duration and low membrane potential in border zone cells between the scar and normal tissue. We studied the basis for these electrophysiological changes by measuring intracellular potassium and sodium activity with ionsensitive microelectrodes in normal, border, and infarct zone cells of the cat left ventricle 2–6 months after ligation of multiple distal tributaries of the left anterior descending and circumflex coronary arteries. In normal zone cells, intracellular potassium activity was 89.6 ± 12.3 mM (mean ± SD,n= 9), and sodium activity was 10.8 ± 2.2 mM (n= 5). Neither was significantly different from infarct zone cells (91.2 ± 15.0 and 10.5 ± 3.0 mM, respectively). In contrast, border zone cells had significantly reduced intracellular potassium activity (71.4 ± 5.1 mM,P< 0.01, compared to normal and infarct zone cells) and increased intracellular sodium activity (19.1 ± 5.9 mM,P< 0.05, compared to normal and infarct zone cells). The membrane potential in border zone cells was more positive to calculated potassium equilibrium potential, and less sensitive to the change in the extracellular potassium concentration in the range between 2 and 10 mM, compared to normal and infarct zone cells. Sixty minutes of exposure to 5 × 10−7M ouabain reduced the membrane potential and intracellular potassium activity to a lesser degree in border zone cells than in normal and infarct zone cells (P< 0.05), but the percent changes from the initial values were not significantly different among the three zone cells. We conclude that action potential changes in infarct zone cells are not accompanied by changes in intracellular potassium and sodium activities, while border zone cell changes are accompanied by reduced intracellular potassium activity and increased intracellular sodium activity. Our data also suggest that border zone cells have altered potassium and/or sodium conductances.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

To determine the mechanical factors affecting regional segmental motion after acute coronary occlusion, we studied seven conscious dogs, instrumented with sonomicrometers Loading conditions were changed by the withdrawal of 500 ml of blood and the transfusion of 800 ml of blood. To express segmental motion, percent systolic shortening, percent systolic elongation, and early diastolic shortening were calculated. Blood withdrawal decreased left ventricular preload, increased percent systolic elongation (from 6.9 ± 3.1% to 9.9 ± 3.5%) and early diastolic shortening (12.9 ± 5.3% to 16.6 ± 5.3%), and decreased percent systolic shortening. Blood transfusion increased left ventricular preload, decreased percent systolic elongation (to 5.2 ± 1.8%) and early diastolic shortening (8.8 ± 2.9%), and increased percent systolic shortening. Manipulation of loading did not change regional myocardial blood flow. In acutely ischemic myocardium, the tension-length loop showed an exponential upstroke during isovolumic systole and a nearly superimposed exponential downstroke during the isovolumic relaxation phase after systole, compatible with essentially passive movement as seen with an elastic material. The changes in loading conditions affected the tension-length curve to a very minor extent. The uniformity of the curve and its exponential shape explain the load-dependency of systolic bulding and segmental motion. It is concluded that systolic bulging depends on the change in the preload tension due to the compliant portion of tension-length curve, and that shortening of ischemic myocardium during the isovolumic relaxation phase is a completely passive phenomenon.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Platelet-activating factor (acetyl-glyceryl-ether-phosphorylcholine; l-O-alkyl-2-Oacetyl-sn-glycero-3-phosphorylcholine), which is released by stimulated neutrophils and platelets, possesses the ability to alter vascular tone and permeability and to activate various formed blood elements. We have characterized the hemodynamic effects of intracoronary injections of plateletactivating factor and the influences of pharmacological blockade and platelet depletion on its activity. Intracoronary injections of platelet-activating factor produced maximum increases in left circumflex coronary artery blood flow of 55 ± 8, 52 ± 8, and 52 ± 7 ml/min at 0.5, 1.0, and 2.0 nM, respectively. Only modest changes in systemic arterial blood pressure and regional developed isometric contractile force were associated with the intracoronary artery administration of platelet-activating factor over the range of doses studied. The increase in left circumflex coronary artery blood flow in response to platelet-activating factor was attenuated (44%), but not prevented, by pretreatment with diphenhydramine, (4 mg/kg, iv), and was not affected by pretreatment with aspirin (20 mg/kg, iv) or the systemic administration of the serotonin receptor antagonist, methysergide. The coronary vasodilator response to platelet-activating factor was reduced significantly by the induction of thrombocytopenia (95 ± 3% platelet depletion) through the administration of sheep-derived canine platelet antiserum. The intracoronary artery injection of platelet-rich plasma activated with platelet-activating factor into thrombocytopenic dogs produced a significantly greater increase in coronary artery blood flow than the injection of either non-activated platelet-rich plasma or platelet-depleted plasma to which platelet-activating factor was added. Similar changes in coronary artery blood flow could be obtained with the intracoronary artery injection of cell-free supernates from washed platelets activated with platelet-activating factor. The observed results suggest that circulating platelets, when exposed to platelet-activating factor, can release a coronary dilator substance, and that the coronary artery dilation is not prevented by pharmacological receptor antagonists for histamine, serotonin, or inhibitors of cyclooxygenase.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

To determine whether accumulation of long-chain acyl camitine contributes to electrophysiological abnormalities induced by hypoxia, we characterized effects of normoxic and hypoxic perfusion on the subcellular distribution of endogenous long-chain acyl camitine and transmembrane potentials of cultured rat neonatal myocytes. Hypoxia increased long-chain acyl camitine more than 5-fold. Sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (10 μM), a camitine acyltransferase inhibitor, precluded accumulation of long-chain acyl camitine induced by hypoxia. Tissue was processed for electron microscopy by a procedure specifically developed for selective extraction of endogenous short-chain and free camitine but retention of endogenous long-chain acyl camitine. In normoxic-perfused cells, long-chain acyl camitine was concentrated in mitochondria and cytoplasmic membranous components. Only small amounts were present in sarcolemma. Hypoxia increased mitochondrial long-chain acyl camitine by 10-fold and sarcolemmal long-chain acyl camitine by 70-fold. After 60 minutes of hypoxia, sarcolemma contained 1.4 × 10<sp>7</sp>long-chain acyl camitine molecules/μm<sp>3</sp>of membrane volume, a value corresponding to approximately 3.5% of total sarcolemmal phospholipid. Hypoxia also significantly decreased maximum diastolic potential, action potential amplitude and maximum upstroke velocity of phase 0. Sodium 2-[5-(4-chlorophenyI)-pentyl]-oxirane-2-carboxylate inhibited accumulation of long-chain acyl camitine in each subcellular compartment and prevented the depression of electrophysiological function induced by hypoxia. These results strongly implicate endogenous long-chain acyl camitine as a mediator of electrophysiological alterations induced by hypoxia.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The contributions of β1-, β2-, and α2-adrenoceptors in the posterior hypothalamus to the increased renal sympathetic nerve activity and decreased urinary sodium excretion resulting from environmental stress (air jet) in conscious spontaneously hypertensive rats were examined. Air stress increased mean arterial pressure and renal sympathetic nerve activity (54% from 7.0 ±0.7 integrator resets/min), and decreased urinary sodium excretion (44% from 2.7 ± 0.4 μEq/min per 100 g body weight). After bilateral injection of ICI 118,551 (β2-adrenoceptor antagonist) into the posterior hypothalamus of the same spontaneously hypertensive rats, air stress had no effect on renal sympathetic nerve activity (8% from 4.8 ± 0.7 integrator resets/min) or urinary sodium excretion (2% from 5.2 ± 0.8 μEq/min per 100 g body weight), but still increased mean arterial pressure. Bilateral injection of isoproterenolol (β-adrenoceptor agonist) into the posterior hypothalamus enhanced the renal sympathetic nerve activity and urinary sodium excretion (but not mean arterial pressure) responses to air stress. Air stress had no effect on renal sympathetic nerve activity or urinary sodium excretion when ICI 118,551 was given into the posterior hypothalamus before isoproterenol. Atenolol (β-adrenoceptor antagonist) had no effect on the renal responses to air stress when given alone or before isoproterenol. Similarly, ICI 118,551 administered into the lateral hypothalamus or lateral cerebral ventricle, or guanabenz (α2-adrenoceptor agonist) given into the posterior hypothalamus, had no effects on the renal or mean arterial pressure responses to air stress. Thus, β2-adrenoceptors in the posterior hypothalamus mediate the increased renal sympathetic nerve activity and antinatriuresis resulting from environmental stress in conscious spontaneous hypertensive rats.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Several reports have shown that electrical and ionic changes occurring in acute myocardial ischemia can be closely mimicked by exposure of tissue to hypoxic, acid-, and glucosefree solutions at elevated [K+]o. In the present work, this approach was chosen to distinguish between the combined effects of hypoxia, substrate withdrawal, and acidosis, and the effects of two different levels of [K+]0, (4.7 mM and 11.5 mM) on intracellular sodium activity and resting membrane potential. Measurements were made with microelectrodes in isolated guinea pig papillary muscles. In normoxia at 4.7 mM [K+]o, intracellular sodium activity was 7.5 mM (±1.9 mM, SD) during stimulation at 1 Hz. Combined hypoxia, substrate withdrawal, and acidosis increased intracellular sodium activity significantly, by 3–4 mM in 4.7 mM [K+]oand by approximately 2 mM in 11.5 mM [K+]o, after 9–10 minutes. Increasing [K+]oin normoxic solution decreased intracellular sodium activity by 1.9 mM (±1.3 mM, SD). The transition from normal (4.7 mM [K+]O) Tyrode's solution to “ischemic solution” (hypoxia, acidosis, substrate withdrawal, 11.5 mM [K+]o) was associated with a small initial increase and a subsequent decrease of intracellular sodium activity. The steady state level after 12 minutes was not significantly different from the level in normal Tyrode's solution. The secondary decrease of intracellular sodium activity coincided with the gradual development of inexcitability and was absent in quiescent preparations. Combined hypoxia, acidosis, and glucose-withdrawal produced a depolarization by 7–10 mV at 4.7 mM and at 11.5 mM [K+]o, probably reflecting cellular potassium loss and extracellular potassium accumulation in the restricted extracellular space. Our results suggest that alteration of intracellular sodium in myocardial ischemia results from two opposing changes: (1) a partial inhibition of the sodium-potassium pump by hypoxia, glucose-withdrawal, and acidosis, and (2) a decrease of passive sodium influx following extracellular potassium accumulation. Moreover, the present results support previous findings that net cellular potassium loss from ischemic cells is not (fully) compensated by an equivalent gain of intracellular sodium.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Tissues from diseased hearts are known to exhibit post-repolarization refractoriness and rate-dependent changes of the refractory period that are often inconsistent with changes in action potential duration. To examine the electrophysiological mechanisms responsible for such rate-dependent changes of the refractory period, a narrow inexcitable zone was created by superfusing the central segments of Purkinje fibers with an ‘ion-free isotonic sucrose solution’. The degree of conduction impairment could be finely regulated by varying the resistance of the extracellular shunt pathway. At intermediate or low levels of block, the refractory period remained unchanged or decreased, respectively, as the rate was increased. At relatively high levels of block, however, we observed marked increases of the refractory period in response to increases in the stimulation rate. The disparity of refractoriness between normally conducting fibers and fibers exhibiting discontinuous conduction characteristics and post-repolarization refractoriness increased dramatically as a function of increasing stimulation rate. With the aid of current clamp techniques, we demonstrate that the differential behavior is due to the interplay between ratedependent changes (1) in the restitution of excitability at the site beyond the depressed zone secondary to changes in passive and active membrane properties and (2) in the intensity of local circuit current provided to that site by activity generated in the segment proximal to the zone of block. Our data suggest that rate-dependent changes of refractoriness in Purkinje tissue are principally governed by attendant changes in membrane resistance.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

The Starling equation, which describes net transvascular liquid flow, does not include the possibility that a reduction in plasma protein concentration may have a direct effect on lung liquid conductance or microvascular protein permeability. Nevertheless, both effects have been reported. Since these results were not predictable, we wondered whether the changes were due to the decrease in plasma protein concentration or to the process by which protein depletion was accomplished (batch plasmapheresis which involves considerable handling of blood). To separate these factors, we did control (sham) and protein removal plasmapheresis in awake sheep by two plasmapheresis methods (batch and continuous-flow). We monitored pulmonary hemodynamks, measured lung lymph flow, and determined protein concentrations in lymph and plasma. We calculated or measured the protein osmotic pressures of plasma and lymph. After control plasmapheresis, lymph flow increased and lymph:plasma protein concentration decreased but had returned to baseline levels by 4 hours. After protein removal plasmapheresis, the changes persisted for 24 hours. However, lung microvascular conductance (filtration coefficient) was not increased, except during the first 4-hour period. The changes in lymph flow and protein concentration ratio are explained using a simple two-pore model. We conclude that, over the range studied, hypoproteinemia does not increase lung microvascular liquid conductance or protein permeability.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

To characterize the hemodynamic factors that regulate stroke volume during upright exercise in normal man, 24 asymptomatic male volunteers were evaluated by simultaneous right heart catheterization, radionuclide angiography, and expired gas analysis during staged upright bicycle exercise to exhaustion. From rest to peak exercise, oxygen consumption increased from 0.33 to 2.55 liters/min (7.7-fold), cardiac index increased from 3.0 to 9.7 liters/min per m2(3.2-fold), and arteriovenous oxygen difference increased from 5.8 to 14.1 vol% (2.5-fold). The increase in cardiac index resulted from an increase in heart rate from 73 to 167 beats/min (2.5-fold), and an increase in left ventricular stroke volume index from 41 to 58 ml/m2(1.4-fold). During low levels of exercise, there was a linear increase in cardiac index due to an increase in both heart rate and stroke volume index; stroke volume index increased as a result of an increase in left ventricular filling pressure and end-diastolic volume index and, to a much smaller extent, a decrease in end-systolic volume index. During high levels of exercise, further increases in cardiac index resulted entirely from an increase in heart rate, since stroke volume index increased no further. Left ventricular end-diastolic volume index decreased despite a linear increase in pulmonary artery wedge pressure; stroke volume index was maintained by a further decrease in endsystolic volume index. The degree to which stroke volume index increased during exercise in individuals correlated with the change in end-diastolic volume index (r= 0.66) but not with the change in end-systolic volume index (r= 0.07). Thus, the mechanism by which left ventricular stroke volume increases during upright exercise in man is dependent upon the changing relationship between heart rate, left ventricular filling, and left ventricular contractility. At low levels of exertion, an increase in left ventricular filling pressure and end-diastolic volume are important determinants of the stroke volume response through the Starling mechanism. At high levels of exertion, the exercise tachycardia is accompanied by a decrease in end-diastolic volume despite a progressive increase in filling pressure, so that stroke volume must be maintained by a decrease in end-systolic volume.

ISSN:0009-7330    

出版商:OVID    

年代:1986

数据来源: OVID