摘要:

The relation between Po2and vessel tone was studied in isolated porcine left descending coronary artery rings. Porcine left descending coronary artery mounted isometrically and equilibrated in Krebs-bicarbonate solution (37°C, pH 7.4, when gassed with 95% oxygen +5% carbondioxide) exhibited spontaneous basal tone. Decreasing bath Po2to 40%, 20%, and 12% elicited sustained increases in basal tension which were reversible, ranging between 10% and 20% of the contraction induced by 40 mM potassium chloride. Further decreases in Po2to near zero (anoxia) resulted in relaxation to baseline. Cyclooxygenase inhibitors indomethacin (5.5 × 10−6M), aspirin (5 × 10−5M), and meclofenamate (10−5M) decreased vascular tone and totally prevented coronary vasoconstriction induced by lowering bath Po2to 12% or 40% but did not affect anoxic vasorelaxation. Neither basal tone nor the vasoconstriction induced by decreases in bath Po2were influenced by the antihistaminergic drug pyribenzamine (105M) or by the α-adrenergic blocker phentolamine (10−6). Isoproterenol (10−9to 10−8M) or an elevation of the bath potassium concentration from 5.9 to 11 mM significantly augmented coronary vasoconstriction induced by lowering bath Po2from 95% to 40%. Elevation of the bath potassium chloride concentration to 40 mM further increased isometric force but inhibited the vasoconstriction in response to decreasing Po2from 95% to 40%. Anoxia relaxed contractions induced by 40 mM potassium chloride, histamine, or ouabain. The data suggest the existence of two distinct oxygensensitive mechanisms in porcine coronary arteries, both of which regulate vascular tone. One is activated at relative high Po2values (10–40%), and the vasoconstriction induced by this mechanism is mediated by vascular prostaglandin synthesis. The other is expressed at low Po2values (near zero), and the depression of mechanical activity by this mechanism may be related to limitation of oxidative energy metabolism. The first mechanism can be augmented by β-adrenoceptor stimulation indicative of an interaction between vascular prostaglandin synthesis and β-adrenergic mechanisms in the coronary artery wall.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

When steady state pressure-flow relations are studied in the circumflex coronary artery, pressure gradients develop between it and other branches of the left coronary artery. To assess the effects of these pressure gradients, we compared the pressure axis intercept and shape of steady state circumflex pressure-flow relations in the presence and absence of gradients after autoregulation was abolished, both in the beating heart and during long diastoles in dogs. We used peripheral coronary pressures and radionuclide-labeled microspheres to assess arterial collateral flow. In the beating heart, interarterial pressure gradients reduced the curvature at low circumflex pressures, and overestimated the mean pressure axis intercept by 7.8 mm Hg (P< 0.05). The results were similar for the pressure-flow relations derived during long diastoles. This overestimation exaggerates the difference between the pressure axis intercept and coronary sinus pressure. The peripheral coronary pressure and microsphere results indicate that these effects are mediated largely by arterial collateral flow.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Elevation of intrathoracic pressure during cardiopulmonary resuscitation generates carotid pressure and flow, but also increases intracranial pressure. This increase in intracranial pressure may limit cerebral blood flow. Therefore, we performed studies designed to quantify the extent of this transmission and to identify the mechanism of transmission of intrathoracic pressure to the intracranial space during cardiopulmonary resuscitation in dogs. Intracranial pressure increased during the chest compression phase of all modes of cardiopulmonary resuscitation tested. During simultaneous compression-ventilation cardiopulmonary resuscitation, change in intracranial pressure (mm Hg) = 0.33 change in intrathoracic pressure (mm Hg) + 2.02 (r= 0.86) and was not significantly different from the relationship observed during conventional cardiopulmonary resuscitation. The magnitude of transmission of intrathoracic pressure to the intracranial space was increased by binding the abdomen and by raising the baseline intracranial pressure. No single route accounted for transmission of intrathoracic pressure to the intracranial space during cardiopulmonary resuscitation. Intracranial pressure fluctuations were unrelated to either carotid arterial or jugular venous pressure, and were found instead to be the result of pressure transmission by blood in non-valved veins and by cerebrospinal fluid. This was determined by three maneuvers. First, obstruction of cerebrospinal fluid flow by ligation of the cervical spinal cord reduced intracranial pressure (P< 0.001) and made the change in intracranial pressure equivalent to pressure changes at the confluence of the intracranial venous sinuses, without affecting pressure changes at the confluence of the intracranial venous sinuses. Second, ligation of the cervical spinal cord and one of the two longitudinal vertebral veins adjacent to the cervical cord reduced the pressure changes in the intracranial space and at the confluence of the intracranial venous sinuses to about 60% of the levels observed when the cervical cord alone was ligated. Thus, the non-valved longitudinal vertebral veins appear to be the vascular channels of critical importance to pressure transmission. Finally, pressure changes in the thoracic cerebrospinal fluid were increased (P< 0.05) by cord ligation, even after exsanguination minimized pressure transmission via blood-filled channels, indicating direct transmission of intrathoracic pressure through intervertebral foramina to the cerebrospinal fluid. Thus, although non-valved veins and cerebrospinal fluid account for transmission of intrathoracic pressure to the intracranial space during cardiopulmonary resuscitation, this pressure transmission is modest except with abdominal binding or under conditions of increased intracranial pressure.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Myocardial fiber orientation undergoes an orderly transition from the epicardium to the endocardium in the left ventricle, with circumferential fibers predominating in the middle one-third of the heart wall. How fibers lying at different depths in the myocardium, running in different directions, interact to produce local deformation is not known. To define the relationship between the orientation of uniaxial myocardial fibers andlocal wall motion, we placed three sets of ultrasonic dimension gauges in the middle one-third of the apex-to-base distance of the left ventricle of nine dogs. One pair was placed in line and two intentionally out of line with the presumed local fiber direction. The relative angle between the gauge and the local myofibers was determined by the use of postmortem radiography and histological techniques. Our results show that in the midwall of the left ventricle, myocardial segment shortening is maximal in the direction of local fibers; the shortening measured by gauges placed out of line with the local fiber axis by more than 30° was significantly less than the actual in-line fiber shortening which occurred. This suggests that functional tethering between midwall fibers and endocardial or epicardial fibers does not play a major role in the pattern of midwall deformation. We also documented that an external reference line can be used to predict midwall myofiber direction. Using this line as a guide, ultrasonic dimension gauges could be placed within an average of 12° (range: 0.5 to 18.5°) from the local fiber axis.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Investigators model noncardiogenic pulmonary hypertension by constricting the pulmonary artery to increase right ventricular afterload. To investigate this model's validity, we compared the right ventricular afterload, quantified as pulmonary input impedance, created by constricting the pulmonary artery and by inducing a pulmonary microvascular injury (with glass beads infused into the pulmonary circulation). The pulmonary injury constriction produced a different right ventricular afterload than the microvascular injury. The constriction increased both the input resistance and the characteristic impedance. Mircrovascular injury increased only input resistance. Physiological levels of lung inflation did not influence pulmonary impedance, but lung hyperinflation increased input resistance both before and while constricting the pulmonary artery or after producing microvascular injury. Total right ventricular power output and stroke work were unchanged during each vascular intervention. Pulmonary artery constriction did not affect power output distribution, whereas microvascular injury decreased oscillatory power and its relative contribution to total power. Lung hyperinflation dramatically reduced right ventricular power and left ventricular stroke work. These effects appeared mediated by right ventricular afterload increase uncompensated for by right ventricular preload increase. These observations help explain the hemodynamic consequences of acute pulmonary hypertension and the effects of lung hyperinflation with positive end-expiratory pressure respiration in such patients.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Theoretical models of oxygen transport in the myocardium have failed to account for low average tissue pO2relative to to coronary sinus pO2, measured with pO2electrodes and myoglobin saturation, and for hypoxic contractile failure at relatively high coronary sinus pO2levels. These findings could be explained by either arteriovenous diffusional shunting or a limiting rate of transfer of oxygen from blood to tissue, or both. To gain new insights, we performed multiple indicator dilution tracer experiments across the coronary circulation in the dog, with18O2as the oxygen tracer and51Cr-labeled red cells as the reference tracer for oxygen.125I-Albumin and22Na+were included to provide the relative plasma flow rate. The tracer oxygen outflow curve consisted of a large early peak related to its reference red cell curve. No tracer emerged before the labeled red cells. The downslope, which contains the returning component of the tracer curve, decreased less steeply when oxygen consumption was reduced by propranolol. Fitting the tracer oxygen outflow curve with a distributed model including irreversible sequestration behind a resistance gave a transfer rate constant which was relatively small, and a relatively large rate constant for sequestration. Relative oxygen consumption (estimated from the arteriovenous difference) correlated closely with the rate constant for sequestration. Estimated average tissue oxygen concentrations were of the order of one-third blood concentration. Dimensional analysis indicates that the low transfer rate constant derives from hemoglobin-oxygen binding; this decreases fractional tracer oxygen transfer in proportion to the ratio of plasma:red cell oxygen pools

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

A new approach to quantifying myocyte cell death utilizing fluorescence-activated sorting of antimyosin antibody-labeled cells was used to study the effects of oxygen-generated free radicals on cell survival. Uptake of antimyosin, reflecting sarcolemmal damage, increased under conditions which promoted elevated free radical formation and decreased in the presence of increased levels of free radical-scavenging agents. Superoxide dismutase decreased antimyosin uptake at pH 6.7 and 7.5. Mannitol decreased antimyosin uptake at pH 6.5 and 6.7 but not at pH 7.5, and dimethyl sulfoxide decreased antimyosin uptake at pH 6.4 but not at pH 7.5. These data suggest that a greater portion of hydroxyl radicals are produced at higher concentrations of hydrogen ion. Mannitol, a scavenger of hydroxyl radicals, was effective in reducing antimyosin uptake at pH 7.5 in the presence of ferrous sulfate, but had no effect on antimyosin uptake in the absence of ferrous sulfate, suggesting possible iron-mediated catalysis of hydroxyl radical formation. The data suggest that oxygen-derived free radicals can cause significant loss of membrane integrity in cultured myocytes, that the species of radical formed is dependent both on pH and the concentration of iron salts, and that this injury is, at least in part, preventable by the administration of exogenous radical scavenging agents

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Hypothyroidism was induced in Wistar-Kyoto rats by adding propylthiouracil to the drinking water (0.8 mg/ml). Initial heat, total activity-related heat, and resting heat rate were measured in left ventricular papillary muscle preparations of propylthiouracil-treated and control rats contracting isometrically at 12 beats/min (21°C), using Hill type, planar vacuum-deposited bismuth and antimony thermopiles. In the propylthiouracil preparations, relative to control, time-to-peak tension increased from 288 ± 27 (mean ± SD) to 411 ± 25 msec (P< 0.001), dp/dtmaxdecreased from 38.3 ± 9.5 to 20.4 ± 3.5 g-mm−2/sec (P< 0.001), and peak developed tension decreased from 6.11 ± 1.75 to 4.64 ± 0.89 g-mm−2(P< 0.05). In the propylthiouracil preparations, initial heat was significantly (P< 0.001) reduced by 27 or 43% when normalized to peak twitch tension or tension-time integral, respectively. In experiments where the papillary muscles were tetanized, the. slope of the linear function of total activity-related heat versus tension-time integral was decreased by 43% (P< 0.001) in the propylthiouracil preparations, indicating an improved economy of isometric tension maintenance. The predominant myosin isoenzyme of the left ventricular wall, as well as the papillary muscle myocardium, was the V3variety in the propylthiouracil animals, in contrast to V1in the controls. Myofibrillar actomyosin calcium-magnesium-stimulated adenosine triphosphatase activity was significantly (P< 0.02) decreased from 55 + 18 (control) to 31 ± 8 nmol inorganic phosphate ion/mg-min (propylthiouracil). Correspondingly, the myofibrillar myosin calcium-stimulated adenosine triphosphatase activity was also significantly (P< 0.01) decreased from 294 ± 98 (control) to 85 ± 25 nmol inorganic phosphate ion/mg-min (propylthiouracil). The results give evidence of (1) increased economy of force generation and maintenance in propylthiouracil myocardium, which is paralleled by (2) structural changes of myosin (shifts in the isoenzyme pattern), and (3) associated changes of myofibrillar adenosine triphosphatase activity. We conclude that the observed myothermal data reflect slowed crossbridge cycling in propylthiouracil myocardium, which must not necessarily be interpreted as being detrimental, in view of the increased economy of force generation.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

Bay k 8644 is a structural analog of nifedipine with positive inotropic activity. The mechanism of drug action was evaluated by measuring the effects of Bay k 8644 on twitch tension, action potential configuration, and calcium channel currents in myocardial cells. Bay k 8644 increases twitch tension in guinea pig atria without changing the time course of tension development. The drug does not occlude the effect of isoproterenol on twitch tension. The effects of Bay k 8644 on atrial twitch tension are highly dependent on the frequency of stimulation. Maximal inotropic effects are observed at ~0.5 Hz, but no inotropic effect occurs at 0.003 Hz (a rested-state contraction). Since positive inotropic effects only occur with frequent electrical stimulation, they are not due to an intracellular action or to mechanisms that elevate cell calcium in quiescent muscle, such as inhibition of the Na, K-ATPase. Bay k 8644 increases the action potential duration of calf ventricular muscle and Purkinje fibers. Effects on action potential duration are occluded by 1 μM nisoldipine, which specifically blocks calcium channels. The interaction of Bay k 8644 with calcium channels in calf Purkinje fibers was studied using the twomicroelectrode voltage clamp technique. Strontium was used as a charge carrier to minimize current through calcium-activated channels and to avoid changes in calcium conductance due to changes in intracellular calcium. Bay k 8644 increases strontium currents and alters the time- and voltage-dependence of channel opening. The greatest percent increase in strontium current occurs for weak depolarizations. For strong depolarizations, strontium current is increased most at the beginning of a test pulse. The drug-induced changes in calcium channel gating are inconsistent with a calcium- or cyclic adenosine monophosphate-mediated effect, and indicate a novel mechanism of action on calcium channels. Thus, Bay k 8644 is the first positive inotropic agent shown to act specifically and directly on calcium channels.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID

摘要:

We have studied the effect of angiotensin II and bradykinin on prostaglandin output and vascular tone during extracellular calcium depletion and administration of calcium antagonists and calmodulin inhibitors to elucidate the mechanism of action in the isolated rat kidney perfused with Tyrode's solution. Administration of angiotensin II (0.028–0.28 nmol) or bradykinin (0.28–2.8 nmol) enhanced the output of prostaglandin E2and 6-keto-prostaglandin F1α, in a dosedependent manner. Angiotensin II, but not bradykinin, produced renal vasoconstriction. Omission of calcium from the medium or infusion of calcium entry blockers, diltiazem (60 μM), or nimodipine (47 μM), failed to alter prostaglandin output elicited by angiotensin II or bradykinin; however, the effect of angiotensin II to produce renal vasoconstriction was inhibited. If calcium was omitted from the medium, the intracellular calcium antagonists, 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (23 μM), dantrolene sodium (31 μM), or ryanodine (2 μM), attenuated prostaglandin output caused by angiotensin II but not bradykinin. Calmodulin inhibitors, trifluoperazine (2 μM), napthalene sulfonamide hydrochloride (2 μM), or calmidazolium (2 μM), diminished prostaglandin output elicited by angiotensin II, but not that caused by bradykinin. Trifluoperazine, but not naphthalene sulfonamide or calmidazolium, attenuated the renal vasoconstrictor effect of angiotensin II. Prostaglandin output induced by angiotensin II and bradykinin were inhibited by mepacrine and indomethacin, whereas, the prostaglandin output caused by exogenous arachidonic acid (33 nmol) was abolished by indomethacin but was unaltered by mepacrine, calcium antagonists, and calmodulin inhibitors. From these data, we conclude that angiotensin II produces renal vasoconstriction by a mechanism dependent on extracellular calcium but not calmodulin, whereas angiotensin II-induced prostaglandin output depends on intracellular calcium and calmodulin. In contrast, bradykinin appears to stimulate prostaglandin synthesis by a calcium/calmodulin-independent mechanism.

ISSN:0009-7330    

出版商:OVID    

年代:1985

数据来源: OVID