摘要:

We investigated how changes in ventricular contractility and arterial properties associated with exercise influence the energy transmission from the left ventricle to the arterial system. On six chronically instrumented dogs preconditioned to run on a treadmill, we imposed exercise loads of various degrees by altering the speed and slope of the treadmill (up to 7 km/hr and 201% slope). We evaluated ventricular contractility by end-systolic elastance (Ees) and arterial properties in terms of the effective arterial elastance (Ea). Eawas estimated by the ratio of mean aortic pressure to stroke volume. With exercise, Eessignificantly increased from 7.6±1.7 to 10.9±2.6 mm Hg/ml (p<0.005), and Eatended to increase from 4.9±1.4 to 6.7±1.8 mm Hg/ml (p=0.068), whereas the ratio of Eato Eesremained fairly constant (from 0.69±0.26 to 0.63±0.21, NS). The mechanical optimality index, defined as the ratio of stroke work to its theoretically derived maximal value, was 0.93±0.07 at rest and 0.92±0.08 at peak exercise. Similarly, the metabolic optimality index, defined as the ratio of cardiac oxygen consumption to stroke work conversion efficiency and its theoretical maximal value, was 0.98±0.02 at rest and 0.99±0.01 at peak exercise (NS). We conclude that external work of the left ventricle of these dogs was at a near maximal level for a given preload during exercise as well as at rest without compromising the conversion efficiency of metabolic energy to stroke work.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

This study tests the hypothesis that arterial vascular stiffening adversely influences in situ left ventricular contractile function and energetic efficiency. Ten reflex-blocked anesthetized dogs underwent a bypass operation in which a Dacron graft was sewn to the ascending aorta and connected to the infrarenal abdominal aorta via a plastic conduit. Flow was directed through either native aorta or plastic conduit by placement of vascular clamps. Arterial properties were measured from aortic pressure-flow data, and ventricular function was assessed by pressure-volume (PV) relations. Coronary sinus blood was drained via an extracorporeal circuit for direct measurement of myocardial O2consumption (MVo2). Data at multiple steady-state preload volumes were combined to derive chamber function and energetics relations. Energetic efficiency was assessed by the inverse slope of the MVO2-PV area relation. Directing flow through plastic versus native aorta resulted in a 60–80% reduction in compliance but little change in mean resistance. Arterial pulse pressure rose from 34 to 99 mm Hg (p<0.001). Contractile function assessed by the end-systolic PV relation, stroke work-end-diastolic volume relation, and dP/dtmaxat matched end-diastolic volume did not significantly change. However, MVo2increased by 32% (p<O.O1) and was matched by a rise in PV area, such that the MVO2-PV area relation and efficiency was unaltered. The MVO2required to sustain a given stroke volume, however, increased from 20% to 40%, depending on the baseline level (p<0.001). Thus, whereas the contractile function and efficiency of normal hearts are not altered by ejection into a stiff vascular system, the energetic cost to the heart for maintaining adequate flow is increased. This suggests a mechanism whereby human vascular stiffening may yield little functional decrement at rest but limit reserve capacity under conditions of increased demand.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The presence of mineralocorticoid receptors (MRs) and their physicochemical characteristics were investigated in the heart and blood vessels of rabbits. Immunohistochemical methods using the monoclonal anti-idiotypic antibody H10E, which interacts with the steroid binding domain of MRs, revealed the presence of immunoreactive material in the heart and large blood vessels. In the heart, a positive staining was observed in myocytes and endothelial cells of atria and ventricles. In vessels, MRs were detected in the aorta and pulmonary artery. They were localized in endothelial and vascular smooth muscle cells. No staining was present in the small vascular bed, arterioles, and capillaries. In all these studies, the mineralocorticoid specificity of the staining was assessed by in situ competition experiments with aldosterone and RU486, a glucocorticoid antagonist. The presence of MRs in the heart and vessels was further demonstrated by specific aldosterone binding to one class of high affinity binding sites in the cytosol of the adrenalectomized rabbit heart (Kd, 0.25 nM; maximum MR concentration, 15–20 fmol/mg protein), whose mineralocorticoid specificity has been clearly established by competition studies. Sedimentation gradient analyses revealed that the cardiovascular MR is an 8.5S hetero-oligomer that includes the heat shock protein 90. The physicochemical characteristics of the cardiovascular MRs are virtually identical to those of the renal MRs. Altogether, our results clearly demonstrate the presence of MRs in the cardiovascular system. This supports the possibility of direct aldosterone actions in the heart and blood vessels.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

An idealized mathematical model was developed to study the effects of variations in conductive and geometric parameters on measured endocardial and intracavitary potentials. The model consists of a spherical multielectrode probe located eccentrically within a system of concentric spheres that represent a blood cavity, myocardium, lung region, and surface muscle layer. Solutions were found for endocardial and intracavitary probe potentials produced by two different configurations of equivalent myocardial sources: 1) multiple activation wave fronts oriented radially, representing global fronts in the myocardium; and 2) pairs of equal and opposite dipoles on a line oriented tangentially to the endocardial surface, representing cardiac sources during early ectopic activation. It was found that the complexities of the cardiac source configurations are reflected in the endocardial potential but not in the associated probe potential, which exhibits a smoothed-out, low-amplitude distribution. In addition, probe potential depends on probe size and location within the cavity. Furthermore, endocardial and probe potentials are influenced by variations in the conductivity of different regions; an increase in blood conductivity results in a decrease in both endocardial and probe potential magnitudes produced by either type of cardiac sources, and an increase in myocardial conductivity results in an increase in both potential magnitudes, whereas an increase in lung conductivity results in an increase in the magnitude of the potential produced by radial sources but a small decrease in the magnitude of the potential produced by tangential sources. The effects of variations in skeletal muscle conductivity are negligible. The volume conductor effects of myocardial anisotropy (9:1 anisotropy ratio) are to attenuate both endocardial and probe potentials by as much as 60% and 71%, respectively, for radial sources and by 96% and 85%, respectively, for tangential sources. In conclusion, volume conductor influences should be considered in the interpretation of measured cavity potentials. Multiple myocardial events are resolved in endocardial potentials but not in potentials measured by an intracavitary multielectrode probe. This observation indicates that for the purpose of resolving cardiac activity, efforts should be directed at inverse reconstruction of endocardial potentials from potentials measured with an intracavitary probe.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We studied the mechanisms underlying the increase in automaticity induced by α1-adrenergic stimulation of normal and “ischemic” canine Purkinje fibers. Fibers were superfused with a control Tyrode's solution, followed by an ischemic superfusate that included 10 mM KCI,5 mM NaHCO3, Po2of 10–25 mm Hg, and pH 6.7. To exclude β-adrenergic actions, propranolol was added to all solutions. In the presence of phenylephrine, normal automaticity at high membrane potentials usually decreased, whereas the incidence of abnormal automaticity during ischemia was increased from a control value of 10% to 30%. Block of an α1-receptor subtype with chloroethylclonidine in the presence of phenylephrine caused normal automaticity to increase in all fibers studied and significantly increased abnormal automaticity to 70%. The α-adrenergic-induced increase in automaticity did not occur in ischemic fibers from animals pretreated with pertussis toxin (PTX), which ADP-ribosylated and functionally inactivated the 41-kd family of GTP regulatory proteins. In contrast, the use of PTX enhanced the increase in automaticity induced by phenylephrine in normally polarized Purkinje fibers. Ryanodine, which blocks sarcoplasmic reticulum Ca2+release, attenuated the increase in normal automaticity in nonischemic fibers but had no effect on abnormal automaticity in ischemic fibers. The increase in abnormal automaticity was, however, blocked by the α1subtype blocker WB 4101, which also blocks the increase in automaticity in normal fibers. In conclusion, the increase in abnormal automaticity in ischemic Purkinje fibers depends on a WB 4101-sensitive α1-adrenergic receptor subtype whose actions are transduced by a PTX-sensitive 41-kd G protein and are not blocked by ryanodine. This is clearly different from the mechanism underlying the increase in automaticity in normal Purkinje fibers, which is independent of the PTX substrate but is suppressed by ryanodine.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Patch-clamp recording techniques have permitted measurement of the fast Na+current (INa) in isolated cardiac cells from a number of species in recent years. However, there is still only very little information concerning human cardiac INa. The purpose of this study was to describe the kinetics of INain normal-appearing, Ca2+-tolerant, enzymatically isolated human atrial myocytes using whole-cell voltageclamp techniques. Atrial specimens were obtained from 46 patients undergoing open heart surgery. Cs+was substituted for K+in both pipette and external solutions and F- was added to the former. The reversal potential of the rapid inward current varied approximately 57 mV at 17±1°C with a 10-fold change in [Na+]., and the current was completely blocked by 100 μM tetrodotoxin, findings typical of the fast cardiac Na+current. The tetrodotoxin dose-response curve was best fitted by an equation describing binding to high- and low-affinity sites. INawas activated at a voltage threshold of −70 to −60 mV, and peak inward current was obtained at ≈ −30 mV (holding potential, −140 mV). The inactivation time course was voltage dependent and was fitted best by the sum of two exponentials. The relation between voltage and steady-state availability (h∞) was sigmoidal with the half-inactivation at −95.8±0.9 mV and a slope factor of 5.3±0.1 mV (n=46), and we did not observe a significant difference with disease and age. The overlap of the h∞ and activation curves suggested the presence of a Na+“window” current. Recovery from inactivation also was voltage dependent and best fitted by a model describing the sum of two exponentials. Recovery occurred after an initial delay at potentials positive to −140 mV, suggesting that inactivation of human atrial INais a multistate process. We conclude that INaof normal-appearing, Ca2+-tolerant human atrial myocytes is similar to that of other mammalian cardiac cells with the possible exception of having two tetrodotoxin binding sites.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Na+-Ca2+exchange has been shown to contribute to reperfusion- and reoxygenation-induced cellular Ca2+loading and damage in the heart. Despite the fact that both [Na+]iand [Ca2+]ihave been documented to rise during ischemia and hypoxia, it remains unclear whether the rise in [Ca2+]ioccurring during hypoxia is linked to the rise in [Na+]ivia Na+-Ca2+exchange before reoxygenation and how this relates to cellular injury. Single electrically stimulated (0.2 Hz) adult rat cardiac myocytes loaded with Na+-sensitive benzofuran isophthalate (SBFI), the new fluorescent probe, were exposed to glucose-free hypoxia (Po2<0.02 mm Hg), and SBFI fluorescence was monitored to index changes in [Na+]i. Parallel experiments were performed with indo-1-loaded cells to index [Ca2+]i. The SBFI fluorescence ratio (excitation, 350/380 nm) rose significantly during hypoxia after the onset of ATP-depletion contracture, consistent with a rise in [Na+]i. At reoxygenation, the ratio fell rapidly toward baseline levels. The indo-1 fluorescence ratio (emission, 410/490 nm) also rose only after the onset of rigor contracture and then often showed a secondary rise early after reoxygenation at a time when [Na+]ifell. The increase in both [Na+]iand [Ca2+]i, seen during hypoxia, could be markedly reduced by performing experiments in Na+-free buffer. These experiments suggested that hypoxic Ca2+loading is linked to a rise in Na+ivia Na+-Ca2+exchange. To show that Na+-Ca2+exchange activity was not fully inhibited by profound intracellular ATP depletion, cells were exposed to cyanide, and then buffer Na+was abruptly removed after contracture occurred. The sudden removal of buffer Na+would be expected to stimulate cell Ca2+entry via Na+-Ca2+exchange. A large rapid rise in the indo-1 fluorescence ratio ensued, which was consistent with abrupt cell Ca2+loading via the exchanger. The effect of reducing hypoxic buffer [Na+] on cell morphology after reoxygenation was examined. Ninety-five percent of cells studied in a normal Na+-containing buffer (144 mM NaCl,n=38) and reoxygenated 30 minutes after the onset of hypoxic rigor underwent hypercontracture. Only 12% of cells studied in Na+-free buffer (144 mM choline chloride,n=17) hypercontracted at reoxygenation (p<0.05). Myocytes were also exposed to hypoxia in the presence of R 56865, a compound that blocks noninactivating components of the Na+current. R 56865 blunted the rise in [Na+]itypically seen after the onset of rigor, suggesting that Na+entry may occur, in part, through voltage-gated Na+channels. These experiments provide evidence that [Na+]irises during hypoxia and leads to cellular Ca2+loading and cell destruction via Na+-Ca2+exchange. Prevention of the rise in [Na+]iduring hypoxia reduces cellular injury in this model. Further studies are required to fully elucidate the mechanisms underlying the rise in [Na+]ithat occurs during hypoxia and ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To test the hypothesis that 5'-nucleotidase activity during ischemia is attenuated by oxygen-derived free radicals, we measured ischemia-induced reactive hyperemic flow, adenosine release, and 5'-nucleotidase activity in dogs (n=62). A 1-minute occlusion of the coronary artery caused reactive hyperemic flow (307±5 versus 92±1 ml 100 g−1min−1at baseline) with increased release of adenosine (14.4±1.4 versus 0.4±0.1 nmol. 100 g−1min−1at baseline). Superoxide dismutase augmented (p<0.001) both peak coronary blood flow (333±6 ml 100 g−1min−1) and repayment (436±12 versus 320±7 ml/100 g in the untreated group). Adenosine release during reperfusion was augmented (22.7±1.9 nmol 100 g−1min−1,p<0.001), and 8-phenyltheophylline completely abolished the enhanced reactive hyperemia. Enzymatic assay of 5'-nucleotidase activity revealed that the administration of superoxide dismutase increases ecto-5'-nucleotidase activity in ischemic myocardium. When an inhibitor of ecto-5'-nucleotidase, α,β-methyleneadenosine 5'-diphosphate, was administered, the effects of superoxide dismutase were completely abolished. Thus, we conclude that 1) the augmentation of reactive hyperemic flow caused by superoxide dismutase is attributed to the enhanced release of adenosine and 2) the enhanced release of adenosine over the untreated controls is attributed to the protection of ecto-5'-nucleotidase activity during ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The oxidative metabolic rate may be disproportionately high compared with contractile function in postischemic reperfused myocardium. To study the potential involvement of intracellular calcium transport in high energy expenditure after reperfusion, we determined in isolated rat hearts the effect of ruthenium red, an inhibitor of mitochondrial calcium transport, on recovery of contractile function and oxidative metabolic rate. Hearts subjected to 60 minutes of no-flow ischemia exhibited, at 15 minutes after the onset of reperfusion, poor recovery of left ventricular pressure development to only 7% of the corresponding value measured in control hearts (p<0.01). However, myocardial oxygen consumption was recovered to 84% of control (p=NS). The ratio of isovolumic contractile performance (expressed as the product of heart rate and left ventricular pressure development) to myocardial oxygen consumption was severely depressed to 6% of control (p<0.01). Supplementation of the perfusate with 6 μM ruthenium red during the initial 40 minutes of reperfusion resulted in a reduction of myocardial oxygen consumption to 65% of the value measured after 15 minutes of reperfusion in hearts reperfused without ruthenium red (p<0.01), despite a threefold increase of left ventricular pressure development (p<0.05). Oxidation of both palmitate and glucose was reduced to a comparable extent by ruthenium red. The ratio of contractile performance to myocardial oxygen consumption increased progressively during infusion of ruthenium red and did not differ further from control hearts after 30 minutes of reperfusion. Cumulative myocardial release of creatine kinase was reduced by 47% (p<0.05) in hearts reperfused with ruthenium red-containing medium. The results provide circumstantial evidence for the hypothesis suggesting that enhanced energy expenditure by intracellular calcium transport may be involved in the mechanisms underlying the dissociation between left ventricular performance and myocardial oxidative metabolic rate early after postischemic reperfusion.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Heparin binds to thrombogenic extracellular matrices as well as to smooth muscle cells of the vascular wall in vitro. The inhibitory effects of heparin on thrombogenicity of the damaged arterial wall were examined in vivo using small mesenteric arteries of rats and a video recording system attached to a microscope. To induce thrombosis, we damaged the vessel wall over a short segment by compression and exposed the media to the blood stream. A platelet-rich thrombus enlarged graduall at the damaged site, occluded the vascular lumen for a short period, and then flowed away. Compression damage induced such thrombus formation several times. Heparin (500 units/ml) was given in three different ways: intravenous and intra-arterial administration (both 300 units/kg) and intraluminal application under stopped-flow conditions (<0.01 ml) for 1–2 minutes with subsequent draining out. Intravenous heparin significantly decreased both the total duration and the number of thrombotic occlusions, whereas intra-arterial heparin abolished thrombotic occlusion. Both routes of heparin administration similarly prolonged the blood coagulation time. Intraluminal application of heparin significantly inhibited subsequent thrombus formation after restoring the flow without changes in the blood coagulation time. After an intra-arterial administration or intraluminal application of fluorescein isothiocyanate-bound heparin, strong fluorescence was observed only at the damaged vascular segment. A heparin fraction with low affinity to antithrombin III or chondroitin sulfate A did not inhibit thrombosis. To clarify anticoagulant activity of vascular wall-bound heparin, damaged carotid arterial segments of rats were incubated (inside out) in platelet-poor plasma with thrombin, and fibrin clot formation around the segments with or without heparin binding was measured. Heparin-bound segments inhibited clot formation. We suggest that heparin inhibits thrombus formation on the damaged arterial wall in vivo not through its anticoagulant action on circulating blood but by its vascular binding and inactivation of the thrombogenic site, for which local inhibition of thrombin activity may be important.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID