摘要:

We have used the sarcoplasmic reticulum (SR) inhibitor ryanodine to assess the contribution of the SR to the increase in twitch tension seen on cooling the mammalian myocardium. To select a suitable concentration of ryanodine, i.e., one that will exert a maximal effect at all temperatures studied, concentration-response curves for ryanodine action were constructed at 37°, 29°, and 23°C in ventricular muscle from rabbit and rat. Using a concentration of ryanodine (1 μM) that exerted a maximal effect at all temperatures studied, the ability of ryanodine to inhibit SR function at 37°, 29°, and 23°C was then confirmed by using rapid cooling contractures (RCCs) to provide an indirect assessment of the SR calcium content. To estimate the rest decay of the SR calcium content in the absence and presence of ryanodine (1 μM), RCCs were initiated after a range of rest intervals (0.3-300 seconds) in rabbit muscles maintained at 37°, 29°, or 23°C. In the absence of ryanodine, low temperatures elevated RCCs at all rest intervals studied. In the presence of ryanodine, RCCs were only seen at rest intervals shorter than 2.0 seconds, even at 23°C, the lowest temperature studied. Thus, even at 23°C, ryanodine appears to be effective at inhibiting SR calcium release in muscles stimulated at 0.5 Hz (i.e., after 2 seconds rest). Therefore, using this concentration of ryanodine (1 μM) and a stimulation rate of 0.5 Hz, we have investigated the contribution of the SR to the positive inotropic response to hypothermia. Under these conditions, the positive inotropic response to cooling in rabbit ventricle was almost unaffected by the inhibition of the SR with ryanodine. In rat ventricle, a tissue in which SR calcium release may dominate excitation-contraction (EC) coupling, the inotropic response to hypothermia was still observed, although developed tension was strongly depressed at all temperatures. These results suggest that a change in SR function is not the principal mediator of the large (400-500%) increase in force associated with cooling mammalian ventricular muscle from 37±to 25°C. The ryanodine-sensitive fraction of tension development was greatest at 37°C, suggesting that the relative contribution of the SR to tension development in rabbit ventricle is reduced at temperatures below 37°C. We investigated the influence of hypothermia on ryanodine-induced changes in action potential in both rabbit and rat ventricle, and the decline in the efficacy of ryanodine at low temperatures cannot be directly attributed to differential electrophysiologic effects at the different temperatures.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Mechanism of coronary spasm was examined regarding endothelium-related relaxation and contraction produced by smooth muscle cells of spastic vessels isolated from Göttingen miniature pigs. In these pigs, coronary artery spasm was documented angiographically in vivo three months after endothelial denudation, and spastic and control segments of the coronary artery were suspended in organ chambers at their optimal length for generating tension. Applications of KC1 (118 mM), acetylcholine(10-9to 10-4M), and PGF2α(10-8to 3 ± 10-5M) produced similar tension, at the respective doses, in both the spastic and control coronary arteries. During increasing concentrations of histamine (l0-8to 3 ± 10-4M; n= 14) and serotonin (10-9to 10-5M; n= 13), the maximum tension of the spastic vessel was 136 ± 6 and 97 ± 4%, respectively, of the tension produced by 118 mM KC1. That is significantly larger than seen in the control vessels: 98 ± 4 and 74 ± 4%, respectively. The ED50to histamine and serotonin was also significantly less in the spastic vessels. After mechanical removal of the endothelium, the tension generated during the cumulative administration of histamine (n = 8) but not serotonin (n = 8) was larger in the spastic than the control vessels, thereby suggesting the presence of augmented responses of the smooth muscle to histamine in the spastic vessels. The increase in maximum tension after mechanical denudation was greater in the control than the spastic vessels in cases of histamine and serotonin. Endothelium-dependent relaxations due to serotonin (n = 5) and A23187 (n = 5) were tested under conditions of precontraction by PGF2α(10-5M). The maximum relaxation induced by serotonin was 31 ± 4 and 67 ± 8% (p<0.01) in the spastic and the control vessel, respectively. A23187 relaxed completely the spastic vessel, to a similar extent as seen in the control vessels; however, the ED50of relaxation evoked by A23187 was 2.7 ± 0.6 ± 10-8and 6.3 ± 1.4 ± 10-9M (p<0.01) in the spastic and the control vessels, respectively. Thus, both increased responsiveness of smooth muscle to histamine and impairment of endothelium-dependent relaxation to serotonin and to histamine may play an important role in the hypercontraction observed in coronary artery spasm in these miniature pigs.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The cardiovascular and respiratory effects of intravenous adenosine were studied in conscious normal volunteers. Bolus injections of adenosine increased systolic and diastolic pressures initially (+15 and +13 mm Hg after 100 μg/kg) followed by a subsequent reduction in systolic and diastolic pressures (-12 and -16 mm Hg). Heart rate increased during trough blood pressure (R-R interval shortening of 298 msec after 100 μg/kg). Adenosine steady-state infusions increased heart rate ( + 30 beats/min during 140 μg/kg/min), systolic pressure ( + 16 mm Hg), and pulse pressure ( + 21 mm Hg) but decreased diastolic pressure slightly (- 5 mm Hg), resulting in no significant change in mean arterial pressure. Adenosine stimulated respiration, resulting in decreased Paco2(41 to 31 mm Hg), increased Pao2(101 to 113 mm Hg), and increased pH (7.42 to 7.50). The increased ventilation was not explained by bronchoconstriction, hypotension, or hypoxia. The observed pressor and tachycardic effects are mediated through reflex autonomic mechanisms since they are completely abolished in patients with severe autonomic failure. These autonomic mechanisms probably involve chemoreceptor activation since adenosine is pressor when infused in the aortic arch proximal to the origin of the carotid arteries but depressor when infused in the descending aorta. It is concluded that the hemodynamic and respiratory effects of adenosine observed in normal volunteers are in part due to chemoreceptor stimulation. These findings raise the possibility that adenosine is an endogenous modulator of respiration in man.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Separan AP-273, a polydisperse, high molecular weight (105-107dalton range), anionic polyacrylamide, demonstrates polymer drag reduction (Toms effect) in the flows of several substances including blood. That is, under appropriate conditions, pipe flow can be increased markedly for a given pressure gradient, sometimes threefold or more, by nanomolar concentrations of linear macropolymers. The effect of intact and degraded Separan was tested in the open-chest, anesthetized rat, and left ventricular and carotid pressures, aortic blood flow (electromagnetic flow probe on ascending aorta), and the electrocardiogram were recorded. The results indicate that aortic flow, which in control animals was about half the flow reported for conscious rats, increases markedly after injection of Separan. The effect on blood pressure after an initial fall was variable, but the slope of arterial diastolic pressure was consistently steepened. Electrocardiographic changes were unremarkable except for a slow decline in heart rate. Although secondary reflexes undoubtedly influenced the results, the primary mechanism of the polymer appears to involve a reduced resistance to flow. The results are compatible with the proposal that the Toms effect, or some variant of it, is operative in vivo under favorable conditions. If this view is correct, then Separan and two other chemically different macropolymers with similar hemodynamic effects and physical attributes, i.e., linearity and molecular lengths approaching 100 μn, might be prototypes of a novel category of cardiovascular drugs.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

In heart failure secondary to chronic mechanical overload, cardiac sympathetic neurons demonstrate depressed catecholamine synthetic and transport function. To assess the potential of sympathetic neuronal imaging for detection of depressed transport function, serial scintigrams were acquired after the intravenous administration of metaiodobenzylguanidine [131I] to 13 normal dogs, 3 autotransplanted (denervated) dogs, 5 dogs with left ventricular failure, and 5 dogs with compensated left ventricular hypertrophy due to a surgical arteriovenous shunt. Nine dogs were killed at 14 hours postinjection for determination of metaiodobenzylguanidine [131I] and endogenous norepinephrine content in left atrium, left ventricle, liver, and spleen. By 4 hours postinjection, autotransplanted dogs had a 39% reduction in mean left ventricular tracer accumulation, reflecting an absent intraneuronal tracer pool. Failure dogs demonstrated an accelerated early mean left ventricular tracer efflux rate (26.0%/hour versus 13.7%/hour in normals), reflecting a disproportionately increased extraneuronal tracer pool. They also showed reduced late left ventricular and left atrial concentrations of tracer, consistent with a reduced intraneuronal tracer pool. By contrast, compensated hypertrophy dogs demonstrated a normal early mean left ventricular tracer efflux rate (16.4%/hour) and essentially normal late left ventricular and left atrial concentrations of tracer. Metaiodobenzylguanidine [131I] scintigraphic findings reflect the integrity of the cardiac sympathetic neuronal transport system in canine mechanical-overload heart failure. Metaiodobenzylguanidine [123I] scintigraphy should be explored as a means of early detection of mechanical-overload heart failure in patients.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The purpose of this study was to examine the movements of Ca2+into the myocardium from the extracellular space during the course of muscle contraction. Equilibration of the rabbit right ventricular wall with perfusate containing45Ca was measured by collecting effluent droplets over time. This protocol was carried out in a quiescent muscle and then repeated 15-20 minutes later in an identical fashion except that halfway through the collection period the muscle was stimulated to contract. We were thus able to quantitate the contraction-dependent changes in45Ca movements. In control experiments using [S8Co]EDTA as an extracellular space marker, we observed that contraction altered the volume of this space. This alteration in extracellular space was relatively small, and the quantitation of45Ca movements was corrected for this change. The addition of 1 μM Bay K 8644 to the perfusate stimulated tension and augmented Ca2+depletion from the extracellular space. The addition of 15 μM nifedipine to the perfusate significantly reduced both tension development and Ca2+depletion from the extracellular space of the muscle. Net contraction-dependent movement of Ca2+from the extracellular space into the myocardium under control conditions at 1 mM [Ca2+] was 10-14 μmol Ca2+/kg tissue wet wt/beat. This value indicates either a large contribution of Ca2+-induced Ca2+release from the sarcoplasmic reticulum and/or significant contribution of sarcolemmal bound Ca2+to excitation-contraction coupling in the rabbit ventricle.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The effects of the discrete cellular structure on propagation of electrical excitation in cardiac muscle were studied in a one-dimensional fiber model containing a periodic intercalated disk structure. Globally, the macroscopic velocity of propagation follows the behavior associated with propagation in a continuous tissue (except for high values of disk resistance). In addition, the computed spatial extracellular potential along the fiber is a smooth biphasic waveform and does not reflect the underlying discrete cellular structure of the tissue. Other results of the simulations demonstrate the discontinuous nature of propagation and the importance of the structure in arrhythmogenesis. Vmaxdisplays a biphasic behavior as a function of increasing intercalated disk resistance. An initial "paradoxical" increase in Vmax(with a simultaneous decrease in conduction velocity) is followed by a decrease that leads to decremental propagation and conduction block. The time constant of the foot of the action potential (±toot) increases monotonically with increasing intercalated disk resistance. An increase in the leakage current to extracellular space brings about a significant decrease in the action potential duration and a loss of the plateau. This major effect is accompanied by a relatively smaller decrease in conduction velocity. Collision of two activation wavefronts results in a significant (100%) increase in Vmaxand a very small (0.6%) decrease in ±toot.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Previous studies have suggested that thyroid hormones influence the number of membrane-bound cardiac adrenoceptors, but their effect on the intracellular distribution of adrenoceptors has not been examined. A plasma cell membrane and a vesicular fraction devoid of membrane markers were prepared from hearts of euthyroid and hyperthyroid rats and were used to compare β- and α-adrenoceptors. During daily injection of I-thyroxine, cardiac hypertrophy developed within 4 days and remained unchanged thereafter. The number of membrane-bound β-receptors increased progressively and plateaued within 2 weeks of thyroxine administration. Vesicular β-receptors, on the other hand, increased more gradually and to a lesser extent so that after 2 weeks of I-thyroxine injection, they constituted a smaller proportion of the total β-receptor population compared to normal rats. In contrast, the number of cardiac α1-adrenoceptors declined rapidly to about 80% of that in euthyroid animals and did not change further for the duration of the study. Membrane-bound and vesicular α1-adrenoceptors were affected to the same extent in hyperthyroidism. During regression of cardiac hypertrophy following cessation of thyroxine administration, α1-adrenoceptors rose rapidly (within 2 days) to normal values while β-receptors declined more gradually to normal levels within 2 weeks. In hypothyroid rats, there was a significant decline in the density of both α1- and β-adrenoceptors, with a shift away from the vesicular fraction. These results indicate that both the total numbers of cardiac adrenoceptors and their distribution between the plasma membrane and vesicular fraction are influenced by the thyroid status.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Previous in vitro studies have demonstrated that coronary artery adrenergic nerves are a principal site of accumulation of 5-hydroxytryptamine released from aggregating platelets. The purpose of this study was to determine whether 5-hydroxytryptamine is accumulated by adrenergic nerves at sites of endothelial damage and platelet aggregation in vivo. Coronary artery 5-hydroxytryptamine content and response to in vitro adrenergic nerve stimulation were studied in dogs 24 hours following balloon catheter-induced intimal injury. 5-Hydroxytryptamine content was significantly increased in the catheter-damaged arteries, and there was a coincident decrease in the content of norepinephrine. The relaxation caused by acetylcholine was abolished in the catheter-injured arteries, indicating loss of this endothelial cell-mediated function. The normal β-adrenergic relaxation caused by nerve stimulation was inhibited, and in some cases, contractions resulted; these effects were prevented by serotonergic receptor antagonists. The sensitivity to exogenously added norepinephrine was unchanged, indicating that the changes in the response to nerve stimulation were not due to an altered smooth muscle response to the native neurotransmitter. These observations indicate that following intimal damage, which produces platelet aggregation on the luminal surface of the blood vessel, 5-hydroxytryptamine can assume a transmitter role in coronary artery adrenergic nerves and thereby cause their dysfunction.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Transient coronary occlusion (15 minutes) does not result in irreversible myocardial injury but is associated with a depression of contractile function sustained for several hours to days (“stunned myocardium”). The defect in the contractile process responsible for this phenomenon has been suggested to be causally related to a reduced energetic state, altered excitation or excitation-contraction coupling, or damaged contractile filaments. The purpose of this study was to attempt to exclude one or more of these hypotheses by evaluating the contractile reserve of reperfused myocardium. Regional subendocardial segment function was measured (sonomicrometry) in a control region and in an area (treatment region) perfused by a carotid artery to anterior descending coronary artery bypass in 13 chloralose-anesthetized dogs. Dose-response curves were constructed from changes in segment shortening (%SS) in response to intracoronary calcium infusion before ischemia and following 5 or 15 minutes of occlusion and reperfusion (30 minutes). Calcium infusion before ischemia resulted in dose-dependent increases in %SS in the treatment area to a maximum value of 36.6% from a preinfusion value of 25.5% (p<0.01), in the absence of changes in control region shortening (23.7%). After 15 minutes of occlusion and reperfusion, treatment area %SS had fallen to a depressed but stable level (46% of preischemic values; p<0.01). Subsequent calcium infusion at the same doses as in the preischemic trial produced increases in treatment segment function with return of shortening to control levels at an intermediate dose. At the highest dose, %SS was 35.4%, which was not different from the maximal value found in the preischemic trial. Alterations in heart rate and left ventricular systolic and diastolic pressures during calcium infusion were minor and similar before and after ischemia. Calcium-induced increases in regional segment shortening above control levels (113% of control) in reperfused myocardium were sustained with continuous infusion (30 minutes) without deleterious effects on subsequent function. These results demonstrate that stunned myocardium in this model retains a normal contractile reserve in response to calcium, suggesting that the mechanism responsible for postischemic contractile dysfunction involves calcium.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID