ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The system mean transit time (Tsys)of the impulse response function describing contrast material transit through the coronary circulation was determined from serial digital angiographic images. The linearity, reproducibility, and relations with regional myocardial perfusion and conventional time-density curve parameters, time to peak concentration (TPC), and exponential washout rate (k) were assessed in a dynamic flow x-ray phantom (n=46) and in six open-chest dogs (/t=102) while coronary flow was altered by stenosis and/or hyperemk stimuli. In the phantom studies, the inverse of the system mean transit time (T±,-1) closely predicted flow/volume (r=0.99, slope=0.99). In dogs, Tsys,-1was independent of the shape of the contrast bolus injection (single or double-peaked), class of contrast agent (ionic or nonionic), the type of hyperemic stimulus (dipyridamole, dipyridamole plus norepinephrine, transient total occlusion, or ionic contrast media), and was highly reproducible between adjacent myocardial regions served by the same artery (r=0.98±0.01). There was a strong correlation between Tsys,-1and regional coronary flow for stenotic and/or hyperemic vessels (r=0.94, distribution volume=14.9 ml/100 g) over a wide range (0-514 ml/min/100 g). Tsys,-1performed better than conventional time-density curve parameters TPC-1and k for predicting phantom flow/volume ratios and regional myocardial blood flow in the dog. These data suggest that both digital coronary angiography and coronary contrast transit can be modeled as linear systems and that impulse response analysis may provide accurate and reproducible estimates of regional myocardial blood flow.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In patch-clamped membranes from neonatal rat cardiocytes, elementary Na+currents were recorded at 19°C for study of the inhibitory influence of several antiarrhythmic drugs including lidocaine, diprafenone, propafenone, and prajmalium on DPI-modified cardiac Na+channels. Diprafenone (20 percent;mUmol/1) and lidocaine (300 fimoUl) induced a voltage- and time-dependent block of reconstructed macroscopic sodium current (INa)The drugs depressed the sustained, noninactivating IN2, component (which reflects the number and open probability of DPI-modified Na+channels) effectively, in a voltage- and time-dependent fashion. Once opened, DPI-modified Na+channels are highly drug-sensitive. Antiarrhythmic drugs (propafenone, diprafenone, and, to a lesser extent, lidocaine) provoke a flicker block, that is, the long-lasting openings are chopped into a large number of short and grouped openings. This indicates rapid transitions between a drug-associated, blocked state and a drug-free, conducting state. The latter has a unitary conductance of 12 pS, very similar to the control value in the absence of antiarrhythmic drugs. The decrease in open time of drug-treated DPI-modified Na+channels is concentration- dependent. Hill coefficients for propafenone of about 1.0 and for prajmalium of about 0.7 were calculated. A blocking rate constant of 6.1±107mol-1sec-1for propafenone, but of 1.5±10' moL-1sec-1for prajmalium was obtained at -30 mV. The unblocking rate constant for propafenone was, also at -30 mV, about twice as large as the unblocking rate constant for prajmalium. The open channel block kinetics are essentially voltage-dependent. The affinity of the channel-associated drug receptor increases on membrane depolarization. The blocking rate constant was inversely related to the number of Na+ions moving through the open channel. It is concluded that the manifestation of this voltage- and Na+-dependent flicker block is intimately related to removal of fast Na+inactivation.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Neuropeptide Y is stored in sympathetic nerve terminals throughout the heart and has direct and indirect effects on cardiac function. Although neuropeptide Y has been shown to be released upon intense (16-30 Hz) cardiac sympathetic stimulation, we sought to determine whether effective quantities of neuropeptide Y were released from cardiac sympathetic neurons under more natural conditions. We recorded arterial pressure and cardiac cycle length in 29 anesthetized dogs. We assessed neuropeptide Y release by measuring the attenuation of vagally induced increases in cardiac cycle length (10 seconds every 2 minutes) after trams of sympathetic stimulation. We examined the effect of constant-frequency sympathetic stimulation (frequencies of 2, 5,10, and 15 Hz, applied for train durations of 1,3, and 5 minutes) on vagally induced chronotropic responses. We also determined the effect of varying the pattern of sympathetic stimulation. Both the magnitude and duration of the inhibition of the vagal effects on cardiac cycle length were augmented significantly by increases in the frequency or duration of sympathetic stimulation. In contrast, the inhibition of the vagally induced chronotropic responses was not significantly affected by changes in the pattern of sympathetic stimulation. We also characterized the role of adrenergic receptors. Phentolamine significantly increased the sympathetically mediated inhibition of the vagal effects on cardiac cycle length, but propranolol had no effect. We concluded that neuropeptide Y release from cardiac sympathetic neurons 1) depends on the frequency and duration, but not on the pattern, of sympathetic stimulation; 2) is evoked even at physiological frequencies (2-5 Hz) of sympathetic activity; and 3) is enhanced by a-adrenergic-receptor blockade, but is unaffected by β-adrenergic- receptor blockade.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Infusion of atriopeptin into humans and animals induces diuresis, natriuresis, hemodynamic changes, and an increase in arterial hematocrit. The objective of the present study was to elucidate the mechanism(s) responsible for the increase in hematocrit in rats given atriopeptin-24 (AP-24). Infusion of AP-24 for 30 minutes increased large vessel and total vascular hematocrits by 10-15percent; while decreasing microvascular hematocrits by 9-26percent; in numerous tissues. Regional vascular permeation by [131I] bovine serum albumin was markedly increased (2-5.6-fold) in many tissues, consistent with a 16percent; decrease in plasma volume. AP-24 infusion had no effect on extracellular fluid volume or the volume of circulating red cells. Vascular resistance was decreased and was associated with a significant increase in blood flow in many, but not all, tissues. In the atrium and in the small and large intestine the percentage decrease in microvascular hematocrit exceeded the increase in blood flow. These observations indicate that the increase in large vessel hematocrit induced by AP-24 infusion 1) is accompanied by a decrease in (microvascular) hematocrit in many tissues, 2) reflects an increase in overall (i.e., total vascular hematocrit), and 3) is the consequence of a decrease in plasma volume resulting from a marked increase in the rate of vascular permeation by plasma constituents in multiple tissues.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Vasoconstrictor responses are augmented in porcine coronary arteries in hypercholesterolemia and atherosclerosis, leading to an occurrence of coronary vasospasm in the latter condition. The role of the endothelium in the vascular hyperreactivity in hypercholesterolemic and atherosclerotic coronary arteries was examined, particularly in response to aggregating platelets and related vasoactive substances. Male Yorkshire pigs underwent balloon endothelial denudation of the left anterior descending coronary artery (LAD) and 2percent; high-cholesterol feeding for 10 weeks. Electron microscopic examination demonstrated a full lining of endothelial cells in the LAD and the left circumflex coronary artery (LCX). Endothelium-dependent responses were examined in vitro. In cholesterol-fed animals, endothelium-dependent relaxations to aggregating platelets, serotonin, ADP, bradykinin, thrombin, and the calcium ionophore A23187 were depressed in LAD (atherosclerosis), while the relaxations to aggregating platelets, serotonin and ADP were depressed in LCX (hypercholesterolemia). Serotonin-induced contractions were endotheliumdependentiy augmented in atherosclerotic LAD; the endothelium-dependent component of the contractions was inhibited by blockers of cyclooxygenase. Bioassay studies demonstrated a depressed release of endothelium-derived relaxing factors) from the atherosclerotic LAD in response to serotonin. These experiments indicate that the endothelium-dependent relaxations to aggregating platelets and related vasoactive substances are severely unpaired in atherosclerosis and moderately impaired in hypercholesterolemia. Since coronary atherosclerosis was induced by a combination of balloon endothelial injury (and regeneration) and high-cholesterol feeding in this study, the combined effects of those factors must account for the severely impaired responses in atherosclerosis. The depressed release of the endothelium-derived relaxing factoids) and the concomitant release of vasoconstrictor product(s) of cyclooxygenase appear to be responsible for the impaired relaxations.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The present study was designed to investigate the anisotropy of systolic chord shortening in the lateral, inferior, septal, and anterior regions of the human left ventricle. At the time of surgery, 12 miniature radlopaque markers were implanted into the left ventricular midwall of the donor heart in 15 cardiac transplant recipients. Postoperative biplane cineradiograms were computer-analyzed to yield the three-dimensional coordinates of these markers at 16.7-msec intervals. In each of the four left ventricular regions, chords were constructed from a central marker to outlying markers, and the percent systolic shortening of each chord was calculated. In each region, chord angles were measured with respect to the circumferential direction (positive angles counterclockwise) and each chord was assigned to one of four angular groups: I. oblique, -45±22.5° or 135±22.5°; II. circumferential, 0±22.5° or 180±22.5°; III. oblique, 45±22.5° or -135±22.5°; or IV. longitudinal, 90±22.5° or -90±22.5°. In the lateral, inferior, and septal regions, respectively, systolic shortening (mean± SD percent;) was significantly greater in Group I chords (19±5percent;, 17±5percent;, and 15±4percent;) than those in Group II (15±5percent;, 12±4percent;, and 11±4percent;), Group III (12±4percent;, 12±5percent;, and 11±4percent;), or Group IV (13±5percent;, 13±6percent;, and 12±5percent;). The anterior region was unique hi exhibiting equal shortening in both Group I and Group n chords (16±5percent;), although the shortening of these chords was significantly greater than that of Group III and Group IV (12±5percent;) in this region. A cylindrical mathematical model was developed to relate longitudinal, circumferential, and oblique systolic shortening to torsional deformation about the long axis of the left ventricle. Torsional deformations measured in these 15 hearts were of sufficient magnitude and correct sense to agree with model predictions. These data suggest that torsional deformations of the left ventricle are of fundamental importance in Unking the one-dimensional contraction of the helically wound myocytes to the three-dimensional anisotropic systolic shortening encountered in the transplanted human heart.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This study investigated the action of the calcium antagonist D600 on calcium channel currents recorded in high barium solution from single, enzymatically isolated smooth muscle cells from the rabbit ear artery using the whole cell configuration of the patch-damp technique. D600 (1-100 μM) was applied by bath perfusion or by a new technique that allowed a concentration jump during the current. Application of D600 at rest (holding potential, -60 mV) did not alter the peak inward current elicited on depolarization, but the activation of the channels led to a marked block and an acceleration of the current decay. The mechanism of block of calcium channels by D600 was studied by using pulse protocols with different pulse length and different interpulse intervals. The results were consistent with the hypothesis that D600 has a low affinity for the calcium channels in the resting state and that they have to pass to the open state before the drug affects the calcium channel current. A fast onset of the calcium channel block by D600 (time constant, 502 msec) could be shown by rapid application of D600 during the sustained current component of the barium inward current. However, experiments did not definitely distinguish whether binding occurred to the open or to the inactivated state (although there was some evidence of a long-Listing binding to an inactivated state).

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The development of cardiac hypertrophy secondary to pressure overload is accompanied by isoformic changes of contractile proteins such as myosin and actin.35S-Labeled complementary RNA (cRNA) probes and in situ hybridization procedures were used for analysis of the regional distribution of newly formed transcripts from α-skeletal actin (α-sk-actin) and β-myosin heavy chain (β-MHC) genes during the early stages of pressure overload. The study was performed in 25-day-old rats submitted to a thoracic aortic stenosis and killed after surgery at times ranging from 4 hours to 3 days. Neither α-sk-actin nor β-MHC messenger RNA (mRNA) was detected in the hearts of normal and sham-operated animals. However, α-sk-actin mRNA accumulated throughout the entire left ventricle as early as 4 hours after aortic stenosis, and by 12 hours was also detected in the left atrium. In contrast, β-MHC mRNA was hardly detectable before day 1, and by days 2-3 was mainly restricted to the inner part of the left ventricle and around the coronary arteries. The absence of spatial and temporal coordination in the accumulation of α-sk-actin and β-MHC mRNAs indicates that different signals and/or regulatory mechanisms are implicated in the induction of the two genes in response to hemodynamic overload.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Malnutrition, as well as malignancy, induces alterations in heart metabolism and performance. Previous studies have implicated adrenergic mechanisms as the cause. The present study was undertaken to investigate if the adenylate cyclase system in the rat heart was affected by malnutrition. Three different animal groups with malnutrition were compared with a control group: rats with acute starvation for 14-percent; hours, rats with protein-calorie malnutrition for 2 weeks, and rats with tumors. Stimulation by β-adrenergic receptors and inhibition by muscarinic receptors of adenylate cyclase activity were not altered by malnutrition. However, conditions used for in vitro adenylate cyclase determinations were, of necessity, not physiological. Neither did the number of β-adrenergic and muscarinic receptors change. When competition-binding experiments were performed, differences comprising agonist affinity and affinity state distribution were noted among the groups. The myocardial β-adrenergic receptors formed a reduced number of high-affinity sites in all groups as compared with the control rats. All high-affinity sites displayed a more than 10-fold increase in affinity toward isoproterenol and an impaired sensitivity to guanine nucleotides except in heart membranes derived from rats starved less than 48 hours. While the protein-calorie restricted and the tumor-bearing rats had myocardial β-adrenergic receptors that were unresponsive to guanine nucleotides, after 48 hours of starvation the rats exhibited an attenuated guanine-nucleotide-induced affinity shift. No changes associated with malnutrition in myocardial membrane levels of the stimulatory guanine-nucleotide-binding protein were detected by cholera-toxin-induced ADP-ribosylation. In competition binding between quinudidinyl benzilate and carbachol, myocardial muscarinic receptors derived from malnourished rats exhibited a three-site affinity distribution whereas control rats displayed a two-site affinity distribution. The observations on myocardial /3- adrenergic and muscarinic receptors in malnourished rats are consistent with alterations in receptor and regulatory guanine-nucleotide-binding protein interaction. Our results point to the possibility of regulating cell functions by modifying coupling mechanisms. In addition, β-adrenergic receptors displayed a considerably increased affinity towards isoproterenol, which fact may contribute to the earlier findings of β-adrenergic hypersensitivity in malnutrition.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID