摘要:

Hemorrhage stimulates endocrine and cardiovascular reflex responses that are appropriate for returning blood volume and pressure to prehemorrhage levels. Fetal sheep respond to hemorrhage with increases in plasma adrenocorticotropic hormone (ACTH), cortisol, and vasopressin concentrations and plasma renin activity, but little is known about the afferent limb of the reflex(es) controlling these responses. Fetal sheep between 128 and 133 days' gestation were chronically prepared with vascular catheters. Five fetal sheep were subjected to bilateral section of the cervical vagosympathetic trunks; six fetal sheep were not vagotomized. Four to six days after surgery, the fetuses were subjected to withdrawal of 10 ml of blood every 10 minutes for 2 hours (130 ml total). Vagotomized fetal sheep responded to the hemorrhage with a greater decrease in central venous pressure than the intact fetuses and a slower restitution of fluid to the vascular space (estimated to be 17percent; of the hemorrhage volume in 2 hours) than the intact fetuses (estimated to be 28percent; of the hemorrhage volume in 2 hours). Both groups of fetuses, however, responded to the hemorrhage with increases in fetal plasma ACTH, cortisol, and vasopressin concentrations and plasma renin activity that were not significantly different. A posteriori analysis of the data by correlation analysis revealed that the fetal ACTH, vasopressin, and renin responses to the hemorrhage were more highly correlated to the changes in fetal arterial pH than to changes in fetal mean arterial pressure or central venous pressure. The results suggest that the ACTH, vasopressin, and renin responses to hemorrhage in the fetus may be mediated by chemoreceptors, not by cardiovascular mechanoreceptors. The results suggest the possibility that the fetal hormonal responses to hemorrhage may be secondary to the acidemia produced by reduced umbilical-placenta! perfusion during the period of hypovolemia.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We studied the response of the renin-angiotensin system (RAS) to a surgically created ventricular septal defect (VSD) in immature ovines and also the role of angiotensin II in the pathophysiology of VSD in the chronically instrumented ovine. Plasma renin activity (PRA) was increased from 2.39±1.1 to 3.78±1.4 ng/ml/hr (p<0.05, n=17) after VSD but not after sham procedure. The change in PRA was positively correlated with the amount of left-to-right shunt through the VSD (r=0.74, p<0.05). Inhibition of angiotensin n effect with saralasin (10 μg/kg/ min) or angiotensin n production with captopril (2 mg/kg) lowered systemic resistance (RJ by 14percent; and 34percent;, respectively (p<0.05), and raised pulmonary resistance (Rp) by 35percent; and 77percent;, respectively (p<0.05). Thirty minutes following captopril, the ratio of pulmonary to systemic flow (Qp/Q±) decreased from 3.31±0.18 to 2.15±0.18 (p<0.05) while total pulmonary flow fell from 7.15±0.38 to 5.92±0.34 l/min/M2 (p<0.05, n=ll). Systemic flow increased from 2.17±0.14 to 2.86±0.33 l/min/M2 (p<0.05) despite a reduction in left atrial pressure (17.3±1.0 vs. 13.0±1.7, p<0.01). Reinfusion of angiotensin n (0.02 μg/kg/min) into the central aorta after captopril returned the hemodynamics to baseline including a rise in Rpand fall in Rp. Exogenous angiotensin II alone (0.08 μg/kg/min) or a threefold stimulation in PRA with furosemide (2 mg/kg) caused little hemodynamic effect. The flow disturbance with a large VSD causes near maximal stimulation/effect of the RAS as indicated by the rise in PRA, the lack of response to further increases in PRA, and the response to exogenous angiotensin II. The RAS appears to promote the pathophysiology of VSD, demonstrated with RAS antagonists, by increasing R±, lowering Rp, and causing a redistribution of left ventricular output to the pulmonary circulation.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Oxygen withdrawal from myocardial cells leads to changes of the transmembrane action potential (mainly action potential shortening), to cellular uncoupling, and to changes of vascular permeability. This study was aimed at the simultaneous measurement of electrical activity and passive electrical properties (extracellular and intracellular longitudinal resistance) in arterially perfused rabbit papillary muscles under different conditions of changed oxygen supply. These included 1) complete anoxia (erythrocyte-free perfusate), 2) hypoxia (Po2between 23–28 mm Hg, erythrocytes present) in the presence and absence of glucose, and 3) normoxia with erythrocyte-free perfusate. Similarly to myocardial ischemia, rapid cellular uncoupling occurred only after an initial stable period of approximately 17 minutes, and it required complete anoxia. The marked shortening of the action potential developed before cellular uncoupling. In six out of eight experiments, the fibers were inexcitable when uncoupling started. In severe hypoxia, no significant change of internal longitudinal resistance was observed over 35–40 minutes. The time course of the extracellular longitudinal resistance was different from the change in intracellular resistance: A marked decrease occurred almost immediately after the onset of oxygen withdrawal. This decrease was followed by a small increase in conduction velocity, which was most likely due to a change in the interstitial compartment (edema). It was observed during anoxic as well as during hypoxic perfusion. We conclude that 1) cellular uncoupling in arterially perfused tissue requires almost complete oxygen lack and occurs with a delay of more than 10 minutes, 2) marked action potential shortening precedes uncoupling, and therefore can not simply be attributed to an increase in free, intracellular calcium, and 3) vascular endothelial function is more sensitive to oxygen withdrawal than the myocyte.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Neonatal ventricular myocytes that were incubated in a well-defined serum-free medium containing 50 mM KCl did not contract and maintained stable cell size, as assessed by the protein/DNA ratio. The present study utilized KCl-arrested cells to examine the effect of constant rates of synchronous contraction in normal [K+]±(4 mM) as a physiological stimulus for myocyte growth. Cell growth increased following the onset of contraction when measured over 3 days. The rate of protein synthesis was accelerated in parallel by contraction, but the rate of protein degradation remained similar to rates in noncontracting cells. The capacity for protein synthesis was estimated by total RNA content and was increased in contracting as compared with KCl-arrested cells. This increase was accompanied by faster rates of RNA synthesis as determined from the incorporation of [3H]uridine into RNA and the specific activity of the cellular UTP pool. The rate of RNA degradation was accelerated during contraction but the difference between the rates of RNA synthesis and degradation resulted in net RNA accumulation of 49percent; after 3 days. These data demonstrated that 1) contractile activity stimulated myocyte growth through an increased capacity for protein synthesis and 2) the increased capacity for protein synthesis involved acceleration of the rate of RNA synthesis. Since enhancement of protein synthetic capacity is a common feature of myocyte hypertrophy in vivo and in vitro, this model can be used to examine the regulation of ribosome synthesis during hypertrophic growth.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Studies of the stellate ganglion and middle cervical ganglion indicate that sympathetic efferent nerve activity can be modified by peripheral excitatory inputs and that these neural connections may function as pathways for a peripheral reflex at the level of the thoracic sympathetic ganglia. This excitatory synaptic input could have a soma in either the central or the peripheral nervous system. A study was designed to determine whether chronic decentralization (3 weeks) of the stellate ganglion in cats would 1) abolish sympathetic cardiac afferent nerve activity recorded at the stellate cardiac nerve and 2) abolish local thoracic reflexes that are generated by stimulation of peripheral nerves. The ansae subclaviae, T3and T4rami, and stellate ganglion were also examined by electron microscopy for the extent of Wallerian degeneration. Afferent cardiac activation of the axon collaterals arising from cell bodies located in the dorsal root ganglia was abolished due to degeneration. However, sympathetic afferent nerve activity from the left ventricular receptors was still present and was recorded from the stellate cardiac nerve in all cats. Cardiac receptors were sensitive to mechanical distortion, increases in the left ventricular pressure, and epicardial application of veratrine hydrochloride. These data imply that 1) cardiovascular afferent input to the stellate ganglion persists following chronic decentralization and 2) the sensory neurons are located in the peripheral sympathetic nervous system. Thus, we find that regulation of the heart occurs in part via thoracic ganglia, independently of the central nervous system.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Electrotonic coupling of cardiac myocytes at gap junctions may influence patterns of conduction in myocardium. To delineate the three-dimensional structure and distribution of intercellular junctions, we analyzed serial ultrathin sections of canine myocardium with transmission electron microscopy and disaggregated myocytes with scanning electron microscopy. Morphometric analysis of left ventricular myocardium sectioned in three orthogonal planes revealed that 80percent; of total gap junctional membrane occurred in large, ribbon-like gap junctions oriented transversely at cell end processes. The remaining 20percent; of gap junctional membrane was contained in small gap junctions located within plicate segments (interdigitating regions of cell-to-cell adhesion) of intercalated disks. In serial ultrathin sections, all gap junctions were contiguous with plicate segments. Thus, true "lateral" gap junctions do not exist in working ventricular myocytes and would not likely be able to withstand shear forces created by laterally sliding cells. Examination of serial plastic sections with light microscopy revealed complex overlapping of myocytes such that individual myocytes were connected at intercalated disks to an average of 9.1 ±2.2 other myocytes. These observations provide an improved understanding of the extent and distribution of cell junctions and should facilitate experimental and model studies of conduction in myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The role of thromboxane A2(TXA2) in the control of O2supply/consumption variables during pacing-induced ischemia was examined using the TXA2receptor antagonist SQ 29,548. Anesthetized, open-chest dogs were subjected to left anterior descending coronary artery (LAD) stenosis that produced significant epcardial S-T segment elevation (12 mV) only when superimposed on atrial pacing. Regional myocardial blood flow was determined using radioactive microspheres, and O2consumption was determined by measuring O2saturation of venous blood draining the ischemic region. The dogs were treated with saline or 0.2 mg/kg+0.2 mg/ kg/hr SQ 29,548, and the effect on ischemia was determined during 5-minute pacing-induced ischemic episodes at 10, 40, and 70 minutes postdrug or saline treatment. SQ 29,548 significantly reduced S-T elevation at 40 and 70 minutes postdrug compared with saline values and at all times measured compared with its paired predrug pace+stenosis values. SQ 29,548 reduced S-T elevation approximately 45percent; compared with its paired predrug values at 70 minutes. SQ 29,548 resulted in a significantly higher subendocardial-to-subepicardial flow ratio (0.70±0.10, p<0.05) compared with saline-treated animals (0.42±0.06), with an overall increase of flow to the ischemic region of approximately 40percent;. This increased flow was matched by a proportional increase in O2consumption without a change in O2extraction. The O2supply/ consumption balance was also unchanged by SQ 29,548 implying that despite the increase in blood flow, the ischemic region was still flow-limited. Thus, SQ 29,548 significantly reduced S-T elevation during pacing-induced ischemia, and this may be due in part to an unproved subendocardial flow.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Shortening of the cardiac action potential during ischemia and anoxia is likely to contribute to the decline in contractility that occurs under such conditions. It has been hypothesized that a decrease in the intracellular ATP concentration ([ATP]1) underlies the changes in the action potential. The recently discovered potassium channel activated at low ATP concentrations might provide the link between action potential shortening and low [ATP]1. However, it has yet to be shown that [ATP]1falls to the range required for channel activation at the time when action potential shortening occurs. We have measured action potentials and [ATP]1simultaneously in isolated ferret hearts during ininbition of both oxidative phosphorylation and anaerobic glycolysis (metabolic blockade). Metabolic blockade caused a rapid decline in cardiac contractility, accompanied by a rapid fall in action potential duration. [ATP]1fell only slightly and remained well above the range where activation of the ATP-sensitive K+channel would be expected to occur. Moreover, rentroduction of glucose to the perfusate led to a substantial recovery in both contraction and in action potential duration, again in the absence of any great change in [ATP]1. These results suggest that the action potential shortening observed in metabolic blockade cannot be explained by the simple hypothesis of K+channel opening as a consequence of a decrease in bulk [ATP]1unless the K±for suppression of channel activity by ATP is very much ingher in intact cells than in any of the patch configurations studied. An alternative explanation is that the channel may be regulated under these conditions by mechanisms other than a change in [ATP]1.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Static muscular contraction in anesthetized animals has been firmly established to reflexly increase arterial pressure. Although group III and IV muscle afferents are known to be responsible for this reflex pressor response, there is no evidence that the stimulation of muscle mechanoreceptors, many of which are supplied by group III fibers, plays a role in causing this contraction-induced reflex effect. To provide this evidence, we recorded renal sympathetic nerve activity in chloralose-anesthetized cats while contracting the triceps surae muscles. We found that static contraction tripled renal nerve activity within three seconds of its onset, an increase that was abolished by cutting the L6and S2dorsal roots. On average, the contraction-induced increase in renal nerve activity was observed 0.8±0.1 seconds after the onset of this maneuver. In addition, intermittent tetanic contractions synchronized renal nerve discharge so that a burst of activity was evoked by each contraction. A similarly synchronized renal nerve discharge was evoked in paralyzed cats by electrical stimulation of the tibial nerve at five times motor threshold, a current intensity that activates group III afferents. We conclude that, in anesthetized animal preparations, mechanoreceptors with group III afferents contribute to the reflex stimulation of renal sympathetic outflow evoked by muscular contraction.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effects of atrial natriuretic peptide (ANP) on transmural myocardial blood flow distribution and the reactive hyperemic response in the presence and absence of flow-limiting coronary stenosis were examined in chronically instrumented conscious dogs. Ten-second coronary occlusion without subsequent flow restriction resulted in marked reactive hyperemic responses (Doppler flow probes), mean flow debt repayment was 481±55percent;. When the 10-second coronary occlusions were followed by a 20-second partial restriction that allowed normal preocclusion coronary inflow, the subsequent reactive hyperemia was significantly augmented, mean flow debt repayment was 938±91percent; (p<0.05). Pretreatment with ANP (3μg/kg) did not alter the flow debt repayment after a 10-second occlusion without restriction (474±30percent;, NS) but attenuated the augmentation of reactive hyperemia resulting from the 20-second inflow restriction, flow debt repayment (613±±66percent;, NS). Regional myocardial blood flow to the ischemic region was measured during restricted inflow after a 10-second coronary occlusion before and after ANP pretreatment. Before ANP, subendocardial flow decreased (0.54±0.04 ml/min/g) and subepicardial flow significantly increased (1.03±0.12 ml/min/g) when compared with the nonischemk zone (subendocardial, 1.03±0.09 ml/min/g; subepicardial, 0.87±0.09 ml/ min/g, p<0.05), indicating maldistribution of the restricted inflow. The resultant subendocardial-to-subepicardial ratio in the ischemic region was significantly decreased when compared with the nonischemic region (0.56±0.03 vs. 1.18±0.04, p<0.05). After ANP pretreatment, subendocardial flow to the ischemic region significantly increased (0.71±0.07 ml/min/g, p<0.05) and the subendocardial-to-subepicardial ratio in the ischemic zone was significantly unproved (0.91±0.10, p<0.05). Myocardial flow measured daring coronary occlusion was not altered after ANP pretreatment, indicating no change in native collateral flow to the ischemic region. Myocardial oxygen consumption, aortic and left ventricular end-diastolic pressures, dP/dt, and heart rates were also not affected by pretreatment with ANP. These data indicate that ANP favorably redistributed blood flow to the subendocardium and reduced subendocardial ischemia after a transient occlusion in the presence of a flow limiting coronary stenosis. The reversal of subendocardial hypoperfusion by ANP hi the absence of alterations of intrinsic vascular reactivity or native collateral flow supports a dilation effect of ANP on the intramural arteries.

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID