摘要:

The maximum amplitude of vector loops formed by summing orthogonally recorded bipolar electrograms has been shown to reflect the direction of activation in cardiac muscle. To investigate whether components of vector loops could provide information about different activation directions in local areas of myocardium, we correlated "instantaneous vectors" with isochronal activation patterns in an in vitro preparation of experimental myocardial infarction. In thirteen 3 mm×3 mm regions studied (from 11 tissues), at least 16 microelectrode impalements with a minimum density of 0.8 mm between sites were made. In seven situations in which notched, irregular, and prolonged duration electrograms were present, vector loops pointed in the same general direction throughout their entire time course. Ln these preparations, microelectrode impalements demonstrated only a single major direction of activation. In five of six areas in which multidirectional vector loops were present, two or more separate local directions of activation corresponded to the directions of the vector loop. Instantaneous vectors were then used to analyze propagation patterns in vivo in 10 animals with 2-4-week-old experimental myocardial infarction. Of 150 sites in the 10 animals, 13% contained more than one major local direction of activation. In 11 markedly abnormal sites, electrograms were recorded during pacing from four sites around the recording probe. When comparing electrogram characteristics from the four sites, a mean difference of 5.9 mV in electrogram amplitude and 19.1 msec in electrogram duration (coefficient of variation, 27% for amplitude and 22% for duration) was found. In only two of the 11 sites was it found that the same number of activation directions occurred from all pacing sites. We conclude: 1) Instantaneous components of vector loops accurately represent local directions of cardiac activation at differing times. 2) Most areas of experimental myocardial infarction have only one major direction of activation despite the presence of abnormal electrograms. 3) In some regions, however, two major local directions of activation can be identified within a relatively local area. 4) Geometric activation patterns in experimental myocardial infarction are markedly dependent on initial activation direction.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Vascular studies in humans have advanced the concept that, during orthostatic stress, cardiopulmonary afferents reflexly regulate vascular resistance in the forearm but exert surprisingly little if any effects on vascular resistance in the calf. In contrast, neurophysiological studies have indicated that unloading of cardiopulmonary afferents during lower body negative pressure evokes comparable increases in sympathetic outflow to the muscles of both the forearm and the calf. The aim of this study, therefore, was to determine if alterations in central venous pressure over the physiological range trigger reflex changes in muscle sympathetic outflow that not only are statistically significant but also are large enough to alter vascular resistance in the calf. To accomplish this aim, we measured calf blood flow with plethysmography and simultaneously performed microelectrode recordings of sympathetic outflow to calf muscles in conscious humans during maneuvers designed to alter the loading conditions of the cardiopulmonary afferents. We found that calf vascular resistance increased by 33 ± 7% (mean ± SEM, p<0.05) during decreases in central venous pressure produced by nonhypotensive lower body negative pressure (LBNP) and decreased by 26 ± 5% (p<0.05) during increases in central venous pressure produced by nonhypertensive infusion of normal saline. These changes in calf resistance were at least as large as the changes in forearm resistance evoked by these maneuvers and were accompanied by parallel changes in peroneal muscle sympathetic nerve activity. We performed additional experiments to determine if the increases in sympathetic vasoconstrictor outflow during LBNP were caused not only by deactivation of cardiopulmonary afferents but also by activation of venoarteriolar reflexes caused by distension of leg veins within the negative pressure chamber. Application of LBNP to only one leg caused comparable increases in sympathetic outflow to both legs. Furthermore, without LBNP, venous congestion alone (i.e., inflation of a congesting cuff on the thigh) had no effect on peroneal muscle sympathetic activity. Thus, activation of axonal or spinal venoarterial reflexes in the leg does not explain the observed increases in muscle sympathetic outflow during LBNP. In conclusion, the present findings strongly suggest that the stimulation of skeletal muscleu sympathetic outflow caused mainly by unloading of cardiopulmonary afferents is an important atonomic adjustment to orthostatic stress. In conscious humans, this reflex sympathetic response is accompanied by vasoconstriction in all of the extremities.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Outward membrane currents were characterized in single coronary smooth muscle cells of adult beagle dogs. The cells averaged 96.4×7.1 fim and had a resting potential of −50.7 mV, an input resistance of 307.9 MΩ, a capacitance of 323 pF, and a calculated membrane surface area of 4,037 μm2. The cells contracted in response to external application of acetylcholine or high K+. In voltage clamp by use of the suction pipette method, outward current began to appear at -50 mV and reached 15.2 nA at 50 mV with a current density of 376.5 μA/cm2. The current was reduced by external tetraethylammonium, Ba2+, and internal Cs+, and its reversal potential had a Nernst relation to external K+concentration. Elevation of external Ca2+(Ca2+0) from 0 to 0.3 mM increased total K+current by up to 300%; elevation of internal Ca2+(Ca2+,) to 5×10−7M by internal perfusion increased total outward current to a similar extent, suggesting a large difference in Ca2+transmembrane sensitivity. Total whole-cell K+current consisted of two components: an initial time-independent current (Ii) followed by a time-dependent current (It. Iiand Itwere through separate K+channels based on differences in a) sensitivity to Ca2+O, b) modulation by an inward Ca2+current, c) current amplitudes and activation kinetics, and d) responses to pharmacological agents. I, was the largest component, measuring 4.5 nA in 0 mM Ca o but increasing to 11.9 nA in 03 mM Ca2+O with a steep 2.5 power function. Itactivated with a biexponential time course; in Ca2+o-free solution, its time course was relatively insensitive to voltage changes but became voltage sensitive in the presence of Ca2+0. Further, such sensitivity was abolished or enhanced by Co2* or Bay K 8644, respectively. We concluded that there are two types of Ca2+-sensitive K+ currents, liand It, in coronary smooth muscle cells. Via an inward Ca2+channel Ca2+0 strongly modulates It, both in amplitude and kinetics.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Whole-cell Ca2+channel currents were recorded from isolated single canine Purkinje and ventricular cells to determine whether there were multiple types of Ca2+channels in these two cell types, as in many other excitable tissues. The experimental conditions were such that currents other than Ca2+channel currents were largely suppressed. The charge carrier was either Ca2+or Ba2+(5 mM). In every canine Purkinje cell studied (n=36), we saw T and L Ca2+channel currents that are similar to their counterparts in other tissues. Neither current was affected by tetrodotoxin (30 fiM), but both were reduced by Mn2+(5 mM). Ni1+ (SO fiM) blocked T more than L current. Nisoldipine (1 μM) apparently abolished the L current but also decreased the T current by 50%. Substitution of Ba2+for Ca2+augmented and prolonged L current but did not affect T current significantly. At 36° C and with 5 mM (Ca2+]0, T current inactivated over a voltage range from -70 to -30 mV whereas L current inactivated between -30 and +20 mY. T current was detectable in only some of the ventricular cells studied (8 out of 12). In these cells the ratio of maximal T current to maximal L current (0.2 ± 0.1, n=S) was lower than the T/L ratio in Purkinje cells (0.6 ± 0.2, n-6). The density of peak L current in ventricular cells (7.5 ± 1.7 pA/pF, n=8) was higher than that in Purkinje cells (4.4 ± 3.4 pA/pF, n=6). Therefore, in ventricular cells the L current is the main Ca2+current whereas in Purkinje cells, the T current also contributes significantly to membrane electrical activity. In Purkinje cells, β-adrenoceptor stimulation by isoproterenol (1 μM) increased L current but did not affect T current. On the other hand, in 70% (7 out of 10) of the Purkinje cells, α-adrenoceptor stimulation by 10 μM norepinephrine (in the presence of 2 μM propranolol) increased the T current. Our observations show that the distribution of the two types of Ca2+channels in canine ventricle is heterogeneous and that the two types of Ca2+channels are modulated by catecholamines by different receptors.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Cardiac lymph from a canine model of myocardial ischemia and reperfusion was examined for evidence of chemotactic activity. Lymph was continuously collected from awake animals before and during a 60-minute coronary artery occlusion and up to 6 hours after the initiation of reperfusion. It was assessed for the ability to activate the following proinflammatory functions in neutrophils isolated from the blood of healthy dogs: 1) morphological changes characteristic of chemotactic stimulation, which were assessed by phase contrast microscopy, 2) orientation of canine neutrophils in a gradient of cardiac lymph, which was assessed in Zigmond chambers, 3) the binding of monoclonal antibodies reactive with CDllb and CD18 adherence gtycoproteins, which was assessed by flow cytometry, and 4) adherence of canine neutrophils to monolayers of canine jugular vein endothelium, which was assessed in vitro by a visual assay. Lymph samples collected after 1 hour of reperfusion in animals demonstrating ECG evidence of ischemia and histologkal evidence of infarction exhibited significant stimulatory activity for each of the functions tested. Shape change-inducing activity was evaluated at more frequent intervals than other functions and was found to peak at 1 hour after initiation of reperfusion and to disappear by 6 hours. In addition, the CDllb/CD18 levels on neutrophils isolated from cardiac lymph collected during reperfusion were significantly greater than neutrophils obtained before or during occlusion. Animals that failed to exhibit evidence of infarction also failed to exhibit increased stimulatory activity in lymph collected during reperfusion, and surface levels of CDllb/CD18 on neutrophils collected from reperfusion lymph were not elevated. This study provides direct evidence supporting the hypothesis that chemotactic activity is generated in ischemic and reperfused myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

During development, the cardiac α1-adrenergic chronotropic response changes from positive in the neonate to negative in the adult. The negative chronotropic effect of a,-adrenergic stimulation in the adult depends on maturation of sympathetic innervation and the presence of a pertussis toxin (PT)-sensitive guanine nucleotide-binding (G) protein. To examine the possibility of a developmental change in coupling of a PT-sensitive G protein to the *,- adrenergic receptor, radioligand binding experiments with the iodinated α1-selective radioligand [l25I]-I-2-[β-(4-hydroxyphenyl)ethylaminomethyl]tetralone ([l25I]-IBE 2254) were performed on membranes prepared from control and PT-treated neonatal and adult rat hearts. Scatchard analysis showed fewer aradrenergic receptors in the adult than in the neonate (168 ± 10 fmol/mg protein in the neonate vs. 124 ± 13 fmol/mg protein in the adult), but similar affinities (equilibrium dissociation constant 124 ± 29 pM in the neonate vs. 140 ± 34 pM in the adult). PT treatment did not alter the results. In both the neonate and adult, 5'- guanylylimidodiphosphate [Gpp(NH)p, 500 μM] shifted the 1-epinephrine competition curve to the right and increased the slope factor toward unity. PT had no effect on the 1-epinephrine competition curve in the neonate. However, in the adult PT itself caused a partial shift in the agonist competition curve, reducing but not eliminating the effect of Gpp(NH)p. Consistent with the results from the binding experiments, PT did not have any effect on the a,- adrenergic-mediated positive chronotropic response in the neonate, whereas in the adult the α1,-adrenergic-niediated negative chronotropic response was completely converted to a positive one after PT treatment. These results indicate the presence of a PT-insensitive G protein in the neonatal and adult rat heart and the acquisition of a PT-sensitive G protein linked to the negative chronotropic response during development.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The aim of this study was to quantify the morphological changes in the arterial wall resulting from poststenotic dilatation (PSD). PSD was produced by placing a split nylon ring around the thoracic aorta of the rabbits at a level of T6-7during a sterile thoracotomy done under pentobarfoital anesthesia. After period of PSD ranging from 1-51 months these rabbits were anesthetized, as were the control animals, and the descending thoracic aorta from the fourth to the eleventh ribs was removed following perfusion fixation with Karnovsky's solution at a constant pressure of 80 mm Hg. The extent of PSD development was variable even though the stenotic ring was the same size in all rabbits. Ultrastructural findings showed degenerative changes of the wall components in the PSD region and were more prominent in the aortas with greater dilatation. Morphometric measurements showed that the PSD was accompanied by a decrease in volume density of both smooth muscle cells (SMCs) and elastin and an increase in collagen and ground substance. These changes were well correlated with degree of dilatation and ratio of internal radius to wall thickness (hence, mean wall stress) but not with duration of PSD. While the number of SMCs per unit volume in the PSD aortas was significantly less than normal (p<0.05), there was no significant change in mean cell volume. Although the reduced muscle mass might be expected to lower the capacity of the vessel to maintain tone, previous results show that this does not occur.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effects of glucose and lactate infusion on palmitate oxidation were compared with the effect of 2-tetradecylg]ycidic acid (TDGA), an irreversible inhibitor of the carnitine acyltransferase I, in nonmoxic canine myocardium. The initial capillary transit retention fraction of [l-11C]palmitate and its fractional distribution between oxidation and esterification in myocardium were measured by the residue detection method after intracoronary tracer injection, as well as by effluent measurements of11CO2, the end product of palmitate oxidation. TDGA reduced the initial capillary transit retention fraction (from 56 ± 13% to 37 ± 6%; p<O.001) and oxidation of palmitate (n=19), as also evidenced by the decrease in the fraction of tracer released as11CO2from 28 ± 5% to 6 ± 3% (p<0.001). Infusion of carbohydrate (glucose or lactate; n=6) reduced "CO2 production from 30 ± 7% to 7 ± 4% (p<0.05) but did not alter the initial capillary transit retention fraction of tracer (59 ± 5% vs. 56 ± 10%; NS). The latter was due to increased esterification into neutral lipids (41 ± 11% of injected palmitate after carbohydrate infusion versus 21 ± 12% in control conditions), as measured from multiexponential curve fittings. When carbohydrates were given after inhibition of palmitate oxidation by TDGA (n =7), the "C tissue clearance kinetics were strikingly similar to those observed after carbohydrate infusion alone. Thus, enhanced metabolic trapping of [l-11C]palmitate in myocardium resulted in initial capillary transit retention fractions that were not different from control conditions (41 ± 5% vs. 48 ± 12%; NS) despite inhibition of oxidation. The results show that the intracellular metabolism of palmitate contributes to the control of its uptake by myocardium. The findings are consistent with inhibition of palmitate oxidation by carbohydrates occurring at the same site as TDGA.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

It was investigated whether endothelium-derived relaxing factor (EDRF) increases cyclic GMP (cGMP) content in platelets passing through the coronary bed. Boluses of washed platelets from healthy human donors were injected into the aortic perfusion line of isolated, saline-perfused rabbit hearts under constant flow conditions (28 ± 2 ml/min). The coronary effluent was collected over 5 seconds, and the cGMP content of platelets was determined by radioimmunoassay. Platelet cGMP amounted to 0.34 ± 0.11 pmol/mg protein after passage through the unstimulated coronary bed. During stimulation with acetylcholine (1 μ.M), it increased to 1.6 ± 0.5 pmol/mg (p<0.01; n=14). Simultaneously, the platelet recovery (measured over 20 seconds after injection) was enhanced (by 45 ± 11%; p<0.01) during endothelial stimulation with acetylcholine. Treatment with the EDRF inhibitor hemoglobin (6 μM) completely abolished the increase in platelet cGMP (p<0.01; n = ll) as well as the enhanced platelet recovery (n=8). Inhibition of EDRF by hemoglobin reduced also the basal platelet cGMP content to 0.17 ± 0.11 pmol/mg (p<0.01). The data indicate that basally released EDRF is able to increase cGMP in platelets during a single passage through the coronary bed. The enhanced recovery of platelets after EDRF stimulation, which coincides with an increase of platelet cGMP, suggests that EDRF plays an important role as inhibitor of platelet activation in the coronary circulation.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Since chronic congestive heart failure syndromes are associated with both elevated circulating levels of angiotensin II and potentially lethal ventricular tachyarrhythmias, we investigated the effect of angiotensin II on voltage-dependent cardiac Na+currents. Single-channel Na+currents in neonatal rat ventricular myocytes were studied using the patch clamp method in the cell-attached mode. Angiotensin II applied outside the patch increased the frequency of opening and rates of activation and inactivation of single-channel Na+currents within the patch. These effects were mimicked by the phorbol ester 12 -O-tetradecanoylphorbol-13 -acetate (TPA) and were prevented by prior incubation with TPA. Therefore, we propose that angiotensin II modulates cardiac Na+currents by a cytoplasmic second messenger, perhaps protein kinase C, and this may predispose toward arrhythmia.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID