ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The fate of gap junctions in dissociated adult myocytes, maintained for up to 22 hours in culture medium, was investigated by semiquantitative analysis of thin sections and by freeze-fracture electron microscopy. Gap junctions in the dissociated myocyte are intact bimembranous structures seen either as invaginated surface-located structures or as annular profiles in the cytoplasm. Surface-located junctions are sealed from the exterior by a sheet of nonjunctional membrane originating (together with the "outer" junctional membrane) from the formerly neighboring cell. Serial sectioning was used to establish that at least part of the annular gap junction population in the freshly isolated myocyte represents truly discrete cytoplasmic vesicles; thus, some gap junctions are rapidly endocytosed after myocyte separation. Analysis of the surfflce-located-to-annular gap junction ratio suggested that no further endocytosis occurred in rabbit and cat myocytes maintained for 22 and 15 hours, respectively. Guinea pig myocytes, by contrast, did appear to continue endocytosis in culture. Analysis of the distance of gap junctional structures from the cell surface suggested that little if any inward migration of gap junction vesicles occurred. Hypoxla had no detectable effect on the internalization or inward movement of gap junctions. The quantity of ultrastructurally detectable gap junction membrane appeared to remain constant over time, as did the incidence of"complex structures" (i.e., annular gap junction profiles with features previously suggested to represent degradation). New gap junction formation was negligible, and a reappraisal of the nature of "complex structures" led to the conclusion that the origin of these structures need not be related to degradation. Taken together, the findings suggest that degradation and disappearance of gap junctional membrane after isolation of the mature myocyte constitute a much slower process than previously believed, and the possibility that the cardiac gap junction protein has a longer half-life than its counterpart in liver remains open.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Acute right ventricular pressure overload shifts the interventricular septum leftward and decreases systolic shortening of the left ventricular (LV) septal-lateral diameter. These changes should alter regional shortening in the LV minor axis. To test this hypothesis, LV minor axis circumferential segment lengths of the septum and anterior, lateral, and posterior walls were measured during pulmonary artery or venae caval constriction in seven open-chest dogs with intact pericardia. Starting at an end-diastolic pressure of 10 mm Hg, venae caval constriction decreased LV end-systolic pressure by 19 ± 6% and stroke volume by 40 ± 15% and produced uniform decreases in systolic shortening and end-diastolic length around the minor axis. However, during pulmonary artery constriction resulting in similar decreases in end-systolic pressure (22 ± 7%) and stroke volume (39 ± 11%), decreases in systolic shortening were significantly larger in the anterior (−34 ± 10%) and posterior (−33 ± 21%) walls than in the septum (−10 ± 9%) or lateral wall (−8 ± 13%). The mechanisms of these large anterior and posterior shortening decreases differed: anterior end-diastolic length decreased more than posterior and lateral end-diastolic lengths, while posterior end-systolic length decreased less than anterior and lateral end-systolic lengths. Similar changes were seen at starting enddiastolic pressures of 5 and 15 mm Hg. Propranolol did not alter this nonuniform response, while pericardiectomy attenuated the regional variations. Thus, changes in LV geometry during acute right ventricular pressure overload are associated with nonuniform regional changes in systolic shortening in the LV minor axis that are enhanced by the pericardium.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, exists as multiple molecular forms that differ in their quaternary structure and mode of attachment to the cell surface. The distribution of the individual molecular forms of AChE in various cardiac regions with distinct anatomical characteristics was investigated. The results confirmed those of others by showing that the total pool of cardiac AChE had a nonuniform distribution in heart that paralleled the distribution of choline acetyltransferase. The rank order of this distribution was right a trial appendage >interatrial septum > left atrial appendage=right ventricle=interventricular septum > left ventricle. Velocity sedimentation in sucrose gradients of extracts from selected cardiac areas showed that four molecular forms were present in all areas but that the proportions of these forms differed as a function of area. The right and left ventricular walls, the apical portion of the Interventricular septum, and the left atrial appendage contained G, and G4(globular) AChE in near-equal proportions, but in the basal portion of interventricular septum, the contribution of G4AChE was greater than that of G1AChE. The right atrial appendage and the interatrial septum had the largest amount of activity attributable to G4AChE and the lowest amount attributable to G1AChE. In all cardiac regions, A12(asymmetric) AChE comprised 8–10% of the total AChE pool. The results of this research show that the composition of the globular AChE pool varies in heart as a function of region and that cardiac regions that have the highest AChE activity and that contain parasympathetic ganglia and nodal areas have different pools of globular AChE molecules than other areas. In addition, it appears that there is a uniform proportion of A12AChE in all areas of rat heart.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The role of the central nervous system in the mechanism (s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the left carotid sinus pressure (LCcsp) at a given value for 20 minutes using a pulsatile pressure control system while at the same time keeping the right carotid sinus pressure (RCSP) at a subthreshold level (approximately 40 mm Hg). At the end of the 20 minutes, the LCcspwas reduced to approximately 20 mm Hg, and a baroreflex (RCSP-mean arterial pressure [MAP]) curve was generated on the right carotid sinus using static-step increases in carotid sinus pressure. At the control LCcspof 100 mm Hg, the RCSP-MAP baroreflex had a threshold pressure (Pth) of 86.6 ± 3.1 mm Hg and a set point pressure (Psp) of 104.7 ± 2.5 mm Hg. Increasing LCcspto 140 mm Hg for 20 minutes caused these parameters for the right carotid baroreflex to increase. Pthand Psp increased by 18.4 ± 4.0 and 14.2 ± 3.0 mm Hg, respectively (< 0.05). The baroreflex curve, therefore, was shifted upward and to the right. Decreasing LCcspto 60 mm Hg caused Pthand Psp to decrease by 24.7 ± 5.0 and 18.1 ± 2 mm Hg, respectively (p<0.05). The baroreflex curve was therefore shifted downward and to the left. The percent of resetting of Pthand Psp was 46 ± 9% and 36 ± 8%, respectively, when LCcspwas 140 mm Hg. These values were 61 ± 14% and 46 ± 5%, respectively, when the LCcsp, was set to 60 mm Hg. These results show that conditioning of the ipsilateral carotid sinus baroreceptors can induce acute baroreflex resetting from the contralateral, unconditioned carotid sinus. This strongly suggests that the conditioning pressure can cause baroreflex resetting by a central mechanism alone without the need for the receptors themselves to be reset.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The aim of the present study was to correlate in cardiomyopathic hamsters with congestive heart failure the levels of atrial and ventricular atrial natriuretic factor (ANF) messenger RNA (mRNA) with immunoreactive ANF (IR-ANF) plasma levels and the relative amount of IR-ANF released by the whole heart versus isolated ventricles in the Langendorff preparation. High-performance liquid chromotagraphy analysis of the forms of ANF present in plasma and in the Langendorff effluent of whole heart versus isolated ventricles was also performed. As previously found for cardiac IR-ANF, the levels of ANF mRNA decreased gradually in atria and increased in an analogous fashion in ventricles with the severity of congestive heart failure. Plasma IR-ANF levels (C-terminal) were more elevated in moderate than in severe congestive heart failure, as were the IR-ANF levels in the Langendorff effluent of the whole heart. On the contrary, the effluent of isolated ventricles from animals in severe heart failure yielded more IR-ANF than that from hamsters in moderate heart failure. Thus, while the isolated ventricles from controls contributed 35.8% of IR-ANF released by the whole heart, ventricles from hamsters in moderate heart failure contributed 17.5%, and those from hamsters in severe heart failure contributed 73.9%. These results indicate that atrial cardiocytes contribute more IR-ANF than their ventricular counterpart in moderate heart failure and that ventricles are a major source of plasma IR-ANF in severe heart failure. Analysis of IR-ANF from plasma and the Langendorff efituent from whole hearts and isolated ventricles revealed that the ventricles are the major source of the propeptide (and of its cleaved products) found in the circulation of cardiomyopathic hamsters. These results suggest that ANF synthesis and secretion do not increase conjointly in atria but do increase in ventricles during congestive heart failure.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Platelet activation is markedly increased during coronary thrombolysis and limits the response to thrombolytic therapy. A possible mediator of platelet activation in this setting is thromboxane (TX) A2, a potent platelet agonist formed in greatly increased amounts during coronary thrombolysis hi man. To address this hypothesis, we examined the role of TXA2in modulating the response to intravenous tissue-type plasminogen activator (t-PA) in a chronic canine model of coronary thrombosis. Reperfusion occurred in 60 ± 5 minutes and was complicated by spontaneous reocclusion. The times to reperfusion and reocclusion were platelet-dependent. Consistent with a role for TXA3 in this process, TXA2biosynthesis, determined as excretion of its enzymatic metabolite, 2,3-dinor-TXB2, was markedly increased during coronary thrombolysis. Furthermore, inhibition of TXA2by aspirin, given alone or in combination with a TXA2/ prostaglandin endoperoxide receptor antagonist, accelerated reperfusion and partly inhibited cyclic flow variations during reperfusion. The delay in reperfusion and reocclusion induced by TXA2appeared to be mediated by platelet aggregation since the F(ab')2fragment of 7E3, a monoclonal antibody to the platelet GPIIb/UIa, also accelerated reperfusion and prevented reocclusion without altering TXA2biosynthesis. These findings suggest that platelet aggregation limits the response to coronary thrombolysis and that platelet activation in this setting is partly TXAj-dependent. {Circulation Research 1989;65:83–94)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

This study was performed to determine if the changes in cellular coupling induced by simulated ischemia were rate-dependent and if they contributed to the rate-dependent conduction slowing that occurs in this setting. We also sought to determine if the known ability of verapamil to prevent ischemia-induced conduction changes might be related to the preservation of cellular coupling. We studied the effects of increasing stimulation frequency from 0.5 to 2.0 Hz on the simultaneous changes in the maximum rate of rise (Vmax) of the action potential upstroke, conduction velocity, and internal longitudinal resistance (r1) determined by the voltage ratio method in superfused guinea pig papillary muscles under conditions of simulated ischemia (SI). When stimulation frequency was 0.5 Hz, 30 minutes of SI caused a 16.5% decrease in Vmax, a 16% increase in r1, and a 12.9% decrease in conduction velocity. When stimulation frequency was increased to 2.0 Hz, 30 minutes of SI caused a 30% decrease in Vmax, a 72.9% increase in r1, and a 21.4% decrease in conduction velocity. Thus, the changes were rate-dependent. Verapamil (1times10−6M) did not influence the changes in these parameters during SI at 0.5 Hz nor the decrease in Vmaxduring SI at 2.0 Hz, but it did prevent the rate-dependent increase in r1. Veraparail also prevented the rate-dependent decrease in conduction velocity induced by SI. Our results suggest that during simulated ischemia the rate-dependent component of the increase in r1, contributes to the rate-dependence of the conduction slowing. Our results also suggest that the effects of verapamil on ischemia-induced conduction changes are mediated, at least in part, by the prevention of rate-dependent cellular uncoupling.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Opiate receptor inhibition causes adrenergic receptor-mediated increases in aortic pressure, cardiac output, and left ventricular contractile function in right heart failure. To study whether the effects of opiate receptor inhibition are mediated by means of an action on the central opiate system, we administered equimolar doses of naloxone hydrochloride and naloxone methobromide (MeBr) and normal saline to heart failure dogs. Chronic stable right heart failure was produced by progressive pulmonary artery constriction and tricuspid valve avulsion. Naloxone hydrochloride caused an increase in mean aortic pressure, cardiac output, left ventricular dP/dt and dP/dt/P, plasma catecholamines, and regional blood flows to the myocardium, quadriceps muscle, kidneys, and splanchnic beds. Plasma β-endorphin and adrenocorticotropin also increased. In contrast, neither normal saline nor naloxone MeBr (which does not cross the blood-brain barrier) affected the systemic or regional hemodynamics or neurohormones. Naloxone hydrochloride was also administered to anesthetized heart failure dogs. Pentobarbital anesthesia removed cortical perception of nociceptive stimulation, reduced the increase in plasma epinephrine, and abolished vasodilation in skeletal muscle that occurred in conscious dogs after naloxone hydrochloride administration but had no major effects on responses of plasma norepinephrine, systemic hemodynamics, or other regional blood flows to opiate receptor inhibition. Naloxone hydrochloride had no effect in sham-operated dogs. The results indicate that the hemodynamic effects of naloxone are mediated by an action within the central nervous system. Furthermore, since pentobarbital anesthesia did not markedly alter the hemodynamic responses to naloxone hydrochloride, the acute salutary effects of opiate receptor inhibition probably are not caused by removal of the antinociceptive effect of endogenous opiolds in heart failure. {Circulation Research 1989;65:103–114)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Activation of the transient inward current (In) by a rise in intracellular calcium concentration ([Ca2+]i) is believed to be responsible for generating triggered cardiac arrhythmias. In this study, the cellular basis of the rise in [Ca2+]ithat activates I-n and aftercontractions in single rat ventricular myocytes was examined. [Ca2+]iwas measured both indirectly by cell contraction and directly with fura-2. Under conditions that caused steady-state [Ca2+]ito increase (i.e., calcium overload) membrane repolarization after a voltage-clamp depolarization resulted in the appearance of In that was similar in many respects to that observed in muiticellular preparations. This In occurred at the same time that [Ca2+]; spontaneously increased and preceded the aftercontraction by 60–90 msec. However, IT, recorded from a single cell was variable in time course and amplitude (unlike that observed in muiticellular preparations). Examination of cell contraction and digital imaging of fura-2 fluorescence showed that In was often associated with propagating regions of increased [Ca2+]i, which arose from discrete sites of origin within the cell. Apparently synchronous aftercontractions could also be associated with multiple propagating waves of [Ca2+]i. The variation in the time course and amplitude of In in single cells appeared to be due to changes in the location and number of sites of origin for the waves of [Ca2+]i. After the first aftercontraction and I-n, desynchronization of the sites of origin of increased [Ca2+]ioccurred, and this resulted in a decrease in the amplitude of In and an increase in its duration. We conclude that the variability seen in single cells arises from changes in the pattern of spontaneous Ca release. Such phenomena will seriously complicate interpretation of muIticellular data, even when [Ca2+], is measured directly.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID