ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

This study was prompted by a conclusion that emerged from experiments by others on mammalian ventricular muscle i.e., that the magnitude of the calcium current (Isi) does not influence contraction on the accompanying beat. In the key experiments, muscles were potentiated with paired pulses, rested for 2 minutes, and then re-stimulated. When Co2+was present during the rest, the first post-rest action potential (and presumably I.i) was depressed but contraction was unchanged. In the present study, we have measured the effect of Co2+on the action potential, Isi, and tension of bovine, cat, and rabbit ventricular muscle. All three parameters were depressed by 1–2 mM Co2+when muscle was stimulated at 20/min. The key experiments of the earlier study were repeated. Co1+(1–2 mM depressed both the action potential plateau and contraction on the first post-rest response. We conclude that the use of Co1+in this type of experiment does not provide evidence against a role for Ij in the modulation of contraction.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The effect of cardiac contraction on coronary arterial flow has been described in terms of an intramyocardiaJ pump, which displaces blood backward and forward during systole and diastole, respectively. Normally, the mean forward flow exceeds, and consequently conceals, this backflow. The main left coronary artery of six anesthetized open-chest dogs was perfused with a Gregg cannula from a constant pressure source via a pcrfusion line containing an adjustable stenosis. At mean left main arterial pressures, Pic, of 65, 90, 125, and 155 mm Hg, the hearts were perfused via different grades of stenosis, while a constant mean perfusion pressure (Pic) distal to the stenosis was maintained. Mean coronary flow was then independent of stenosis grade. However, with increasing stenosis grade, the systolic-diastolic coronary flow difference decreased, whereas the dlastolic-systolic coronary pressure difference increased. By varying the stenosis grade at constant Piclinear relationships between diastolic-systolic pressure difference and flow difference were obtained and were interpreted as being a result of an electrical analog potential-source equivalent. From the potential-source equivalent, the diastolic-systolic pressure changes of the intramyocadial pump, pin, can be determined as well as the coronary resistance, Rcimpeding the flow variations originated by pin. We found pin= 53.1 ± 7.02 (SD) nun Hg, and independent of Pic.cwas correlated with the resistance to coronary flow, Rcvia Ra= 0.63 × Rc– 12.9 mm Hg»s/ml (r = 0.939, n = 25). Rcwas defined as (Pic- 14 nun Hg)/mean coronary flow. The waterfall model extended to allow for autoregulation to achieve an equal division of mean flow over the myocardium could not explain these results. From a decay curve of coronary arterial pressure following clamping of the perfusion line, intramyocardial coronary capacitance was estimated to be approximately 0.07 ml/mm rig/100 g LV. This value is in agreement with published volume pressure relationships of the intramyocardial blood compartment. The phasic coronary blood flow component requires intramyocardial arterial volume. We conclude that systolic-diastolic variations in coronary blood flow are not due to varying resistances but are caused by an active intramyocardial pump. Circ Res 49.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

In order to assess the effects of increasing myocardial metabolic demand on the large epicardial coronary arteries, we measured left circumflex coronary artery diameter (ultrasonic transit time technique) and blood flow in conscious dogs with chronically implanted transducers. Myocardial oxygen consumption was increased by pacing-induced tachycardia and aortic constriction, and monitored by multiplying left circumflex coronary arterial blood flow by coronary arterio-venous oxygen content difference. Increase of heart rate by 90 beats/min caused myocardia] oxygen consumption to increase by 34 ± 4.3% (1 SEM); coronary blood flow at constant arterial pressure to increase by 32 ± 6.8%; and coronary diameter to increase by 0.07 ± 0.01 mm, P < 0.01. Aortic constriction, producing a 53 ± 5.1% increase of left ventricular systolic pressure, caused myocardial oxygen consumption to increase by 49 ± 7.2%, coronary blood flow to increase by 50 ± 6.0%, and coronary diameter to increase 0.13 ± 0.03 mm, P < 0.01. The increases in coronary artery diameter were gradual, not immediate, in onset and not altered by β-adrenergic blockade. Thus, increased myocardial metabolic demand dilates large epicardial coronary arteries, but with a slower response time than the rapid dilation of the smaller resistance vessels.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

To investigate the spread of contraction in the rabbit ear artery, changes in segment diameter were measured after local stimulation. No spread of contraction was produced by direct current or local application of norepinephrine (NE). Repetitive electrical stimulation caused contraction which spread far from the point of excitation. Since 2 × 10−7g/ml tetrodotoxin (TTX) or 103M phentolamine prevented this spread of contraction, we concluded that it depends on normal function of periarterial nerves and of the a-adrenergic receptors at the site of the smooth muscle cells. To check this conclusion and exclude the possibility of myogenic propagation, which normally is due to the conduction of action potentials, the relation between membrane potential of smooth muscle cells and the rapid phase of the contractile response after rapid addition of NE was investigated. In both polarized and depolarized tissues NE induces a biphasic contractile response with no difference in latency. Membrane potential does not change during mechanical latency after the rapid addition of 5 × 10−9- 5 × 10−6g/ml NE. There are only slight differences in contraction amplitude and maximum rate of tension development when strips from polarized and depolarized tissues incubated in Ca1+-free solution are stimulated by NE. These findings support the conclusion that spread of contraction is not due to myogenic propagation.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We studied the effect on protein degradation of agents that alter intracellular adenosine 3′,5′-monophophate (cyclic AMP) in isolated rat right atria. Protein degradation rate was determined by measurement of the rate of release of L-tyroslne from atria cultured in the presence of cycloheximide. Stimulation of adenylate cyclase activity by either L-isoproterenol, glucagon, prostaglandin Ei, prostaglandin E2 or cholera toxin produced a 23–43% decrease in tyrosine release rate. L-Isoproterenol (1 fiM) lowered the protein degradation rate both in the presence (27 ± 3%) or absence (25 ± 2%) of insulin. In constrast, the a-adrenergic agonist methoxamine (10 JIM) increased the rate of tyrosine efflux. The phosphodiesterase inhibitors papaverine (0.1 mM) and theophylline (1 mM) reduced tyrosine release rate by 62 ± 2% and 25 ± 2%, respectively. The cyclic nucleotide analog dibutyryl cyclic AMP produced a 23 ± 4% reduction in tyrosine efflux rate, an effect that may be in part due to butyrate released by hydrolysis. Both carbamylcholine and nitroprusside, agents which activate guanylate cyclase, had no apparent effect on the rate of overall protein degradation. In experiments with atria labeled in vitro with radioactive tyrosine, the degradation rate of soluble cell proteins fractionated by gel filtration was uniformly decreased by L-isoproterenol over a wide molecular weight range. Comparison of degradation rate to protein kinase activation, high energy phosphate levels and beating rate show that suppression of degradation is more closely correlated with mechanical activity or energy depletion than with cyclic AMP content. Therefore, these data do not establish whether cyclic AMP modifies protein degradation directly, or by effects secondary to increased contractile activity.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

To determine the effects of healed myocardial infarction on the diastolic compliance of the left ventricle, we studied 36 rats 26 days after left coronary artery ligation. Peak cardiac output and stroke volume were measured under ether anesthesia during volume loading, and peak left ventricular developed pressure was determined during occlusion of the ascending aorta. During a slow infusion of saline into the potassium-arrested left ventricle, diastolic pressure and volume were measured continuously over the pressure range −5 to 30 mm Hg. Infarct size was determined by planimetry of serial sections taken from each heart at 1-mm intervals from apex to base. In rats with healed infarets, left ventricular volume was increased in proportion to infarct size and the diastolic pressure-volume relationship was shifted ao that at pressures below 2.5 mm Hg volume was increased, resulting in an increased ventricular compliance in this low pressure range. Above this pressure, the slopes of the pressure-volume curves were similar in rats with and without infarctions. Peak cardiac output and pressure-generating capacity were impaired in proportion to infarct size. This impairment of cardiac performance correlated with the infarct size-related increase in diastolic volume, which served to offset the reduction in flow generating capacity caused by systolic dysfunction, while contributing directly to the impairment of pressure generating capacity.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We studied hypertensives with decreased adrenal responsiveness to infused angiotensin II (All) to assess their responsiveness to other aldoaterone secretagogues, ACTH and potassium, which are thought to stimulate aldosterone synthesis in sites different from one another and from All. All subjects, following sodium restriction, received an infusion of AH in increasing doses (0.1–3 ng/kg per min). The increment in aldosterone between control and the highest infusion dose divided by the increment in plasma AH was used as the index of adrenal responsivenss. All normotentive controls (NC) had a ratio greater than 0.5. Hypertensives with a normal ratio were designated normal respondera (NR) and those with a lower ratio were abnormal responders (AbR). The slope of the regression line between aldosterone and All was significantly less for the AbR (0.02 ± 0.04) than for the NR (1.20 ± 0.02, P < 0.001) and the NC (1.00 ± 0.03, P < 0.001) groups. During infusion of cosyntropin in increasing doses (0.05–1.5 mlU/kg per 30 min), the aldosterone response of the AbR was significantly less than that of the NR (P < 0.018) or the NC (P < 0.05) groups. Similarly, after infusion of potassium (0.33 mEq/ min), the increment in aldosterone in the AbR group (7.6 ± 2.2 ng/dl) was significantly less than that in the NR (14.2 ± 2.5 ng/dl, P < 0.05) and the NC (18 ± 5 ng/dl, P < 0.05) groups. Thus hypertensives with decreased aldosterone responsiveness to infused All also had decreased responsiveness to infused ACTH and potassium, suggesting that their defect lies in the intracellular aldonterone blosynthetic pathway.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Reoxygenation of hypoxic isolated cardiac muscle results in prolonged duration of contraction–relaxation. To determine whether similar mechanical changes occur in the intact left ventricle (LV), and especially to assess the influence of prolonged relaxation on LV diastolic stiffness, we examined LV pressure transients (micromanometer) and changes in myocardial segment length (ultrasonic transit time) during reoxygenation in 22 anesthetized dogs following 15 minutes of hypoxia (Pao, - 21 ± 2 mm Hg). The time constant (T) of LV isovolumic exponential pressure decline was used as an index of myocardial relaxation; LV end-diastolic stiffness was assessed from stiffness constants derived from multiple coordinates of end-diastolic pressure and segment length (volume loading). During reoxygenation, after LV systolic pressure and segment length measurements had returned to control levels, relaxation was prolonged; T increased from a control of 32 ± 2 to 44 ± 3 msec at 5 minutes of reoxygenation (P< 0.01). Prolonged relaxation resulted in a consistent increase in LV earlydiastolic pressures. Furthermore, calculated values for LV end-diastolic stiffness increased during reoxygenation when the next beat began less than 3.5 T after maximum negative dP/dt; this condition was present more frequently at a heart rate of 150 beats/min than at 120 beats/min. Thus, rapid correction of acute hypoxia in the dog results in prolonged LV relaxation; prolonged relaxation can influence LV end-diastolic stiffness when relaxation is sufficiently slow and/or when diastole is sufficiently short.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The isolated arterially perfused interventricular rabbit septum was adapted for the study of glucose metabolism during ischemia produced by either increased oxygen demand or altered coronary flow. The septum perfused at 1.5 ml/min and stimulated at a rate of 72/min at 37 °C was shown to be a low work preparation in which glucose utilization, lactate production, oxygen consumption, and developed tension were stable for at least 90 minutes. The metabolic and functional responses of the septum were evaluated during nonnoxic increased work produced by introducing a paired stimulus at 90/min and increasing flow to 3.5 ml/min, during demand-induced ischemia produced by introducing a paired stimulus at 90/min and maintaining flow at 1.5 ml/min, and during low flow ischemia produced by decreasing flow and maintaining stimulus rate constant at 72/min. During nonnoxic increased work, glucose utilization increased by 115 ± 26% (±SKM) over control, while oxygen consumption increased by 100 ± 11%, lactate production by 13 ± 9%, and developed tension by 45 ± 8%. Tigsue glycogen, lactate, and lactate:pyruvate ratios were unchanged compared to control. During demand-induced ischemia, glucose utilization increased by 116 ± 24%, while oxygen consumption increased only by 29 ± 7%, lactate production rose by 106 ± 16%, and developed tension declined by 20 ± 4%. Tissue glycogen content was significantly decreased and tissue lactate and lactaterpyruvate ratios were significantly increased during demand-induced ischemia compared to both control and nonnoxic increased work. These results are consistent with accelerated glucose oxidation during nonnoxic increased work and accelerated anaerobic glycolysis during demand-induced ischemia. During severe low flow ischemia, glucose utilization declined by 44 ± 8% while developed tension and oxygen consumption decreased by 80 ± 8% and 74 ± 2%, respectively. The results of this study suggest that the dependence of glucose metabolism in ischemia on residual perfusion for washout of metabolic end products is also observed when ischemia is produced by excessive oxygen demand.

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID