Facial nerve palsy in the newborn.
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Facial Paralysis↗
Biomedical subjects
W J Powell
Publications and source records attributed to W J Powell.
Hyperosmotic mannitol and collateral blood flow to ischemic myocardium.
Elevation of extracellular osmolality reduces the extent of myocardial and endothelial cell swelling that accompanies acute ischemia, and the reduction of cell swelling is associated with an increase in collateral blood flow to the ischemic area. However, little is known about the effects of hyperosmolality on the vascular resistance of the collateral coronary vasculature. We compared the effects of hyperosmolar mannitol with those of nitroglycerin and dipyridamole on the vascular resistance of large collateral coronary vessels and of the small arterial vasculature in an isolated heart model of regional ischemia. Elevation of osmolality by mannitol increased collateral blood flow to the ischemic region through at least two mechanisms. First, increasing osmolality resulted in dilation of large arterial conductance vessels, similar to that produced by nitroglycerin. In addition, mannitol produced an effect on the coronary circulation at a microvascular level which, per se or in combination with its effect on larger collateral conductance vessels, increased collateral blood flow to ischemic regions.
Animals↗
Prostacyclin and pathogenesis of hemodynamic abnormalities of diabetic ketoacidosis in rats.
The pathogenesis of the hemodynamic abnormalities of diabetic ketoacidosis (DKA) is not well understood. Previous studies suggest that prostacyclin (PGI2) production by adipose tissue is increased in DKA. We investigated the role of PGI2 in the pathogenesis of the reduced vascular resistance in DKA. Rats with streptozocin-induced DKA were anesthetized with pentobarbital sodium, and flow was measured with an electromagnetic probe on the infradiaphragmatic aorta. The plasma level of 6-keto-PGF1 alpha (stable derivative of PGI2) was higher (mean +/- SE 0.91 +/- 0.05 ng/ml) and vascular resistance lower (4.9 +/- 0.2 mmHg.ml-1.min-1.100 g-1 [resistance units, RU]) in 67 rats with DKA than in 21 normal rats (0.34 +/- 0.03 ng/ml, P less than .01, and 9.0 +/- 0.7 RU, P less than .01, respectively). Inhibition of cyclooxygenase activity with either indomethacin or meclofenamic acid reduced the plasma 6-keto-PGF1 alpha level but failed to raise vascular resistance. Infusions of PGI2 in rats with DKA demonstrated that the vasculature was responsive to PGI2. Inhibition of cyclooxygenase activity not only reduced PGI2 production but also suppressed renin release. When the effects of the renin-angiotensin system were excluded by bilateral nephrectomy, indomethacin caused a significant increase (P less than .05) in vascular resistance. Thus, the failure of cyclooxygenase inhibitors to raise vascular resistance in DKA was a result of concurrent suppression of vasodilator (PGI2) and vasoconstrictor (renin-angiotensin system) mechanisms that are activated in DKA. Insulin administration increased vascular resistance (P less than .01) and decreased the level of plasma 6-keto-PGF1 alpha (P less than .01). Combined administration of PGI2 and insulin did not alter vascular resistance, suggesting that the increase in vascular resistance with insulin was predominantly due to the reduction of circulating PGI2. Thus, vascular resistance is decreased in DKA primarily as a result of the vasodilator effects of PGI2 produced by adipose tissue. The activation of the renin-angiotensin system represents a partial compensation. The increase in PGI2 production may contribute to the hypotension and mortality of DKA.
6-Ketoprostaglandin F1 alpha↗
Effect of intracarotid administration of ouabain in dogs.
Recent work has documented both centrally mediated vasoconstriction and, paradoxically, a withdrawal of sympathetic activity in response to cardiac glycosides. In the present study the possibility that these different neurogenic responses might be dose related was investigated by infusing ouabain (5, 10, and 20 micrograms) for 5 min into the right common carotid artery of 51 anesthetized mongrel dogs. Effects on vascular resistance in the isolated, separately perfused but innervated gracilis muscle were measured. A 5-microgram infusion of ouabain (n = 6) produced a prolonged decrease in gracilis vascular resistance (GVR) of 19.4 +/- 5.4% (SE) from 43.4 +/- 6.7 (SE) to 33.7 +/- 4.2 mmHg.ml-1.100 g muscle.min (resistance units, RU). This vasodilatory response was not present in nine additional dogs following denervation of the carotid bifurcation. A 10-microgram infusion had no significant effect on GVR (n = 5), but the 20-microgram infusion of ouabain (n = 8) caused a rapid increase in GVR from 42.1 +/- 5.0 to 47.6 +/- 5.7 RU, an increase of 14.4 +/- 5.6%, which was not influenced by denervation of the carotid bifurcation (n = 8). This vasoconstriction was transient returning toward the control levels by 20 min following the infusion. These data indicate important dose-related differences in vascular responses to ouabain that are directionally opposite and mediated by separate neurogenic mechanisms. At high doses a centrally mediated vasoconstriction dominates, whereas at low doses carotid bifurcation mediated vascular dilatation occurs.
Animals↗
Direct effects of alpha 2-adrenergic receptor stimulation on intravascular systemic capacity in the dog.
The role of alpha 2-adrenergic receptor stimulation in the regulation of systemic vascular capacity and venous return, a major determinant of cardiac output, is not well understood. With the influence of the central nervous system isolated from the systemic circulation, the direct peripheral vascular effects of two specific, chemically distinct alpha 2-adrenergic receptor agonists, UK 14,304 and B-HT 920, were investigated in 19 dogs on total cardiopulmonary bypass with constant arterial perfusion and central venous pressure. Five-minute intra-arterial infusions of UK 14,304 (200 micrograms/min) resulted in increased arterial resistance (mean arterial pressure increased 18 +/- 4 [SEM] mm Hg; p less than 0.01) and a decrease in systemic vascular capacity (81 +/- 20 ml; p less than 0.01). This decrease in systemic vascular capacity appears to result from vasoconstriction, since there was no decrease in transhepatic resistance to portal flow and no significant change in hepatic vein flow to suggest redistribution of arterial blood flow. Yohimbine abolished both the arterial and systemic capacity effects, whereas prazosin did not. Intra-arterial administration of B-HT 920 (200 theta grams/min) in five dogs produced similar changes in arterial resistance and systemic capacity. These findings provide direct evidence for beta 2-adrenergic control, not only of arterial resistance but also of systemic vascular capacity, which in the intact animal would increase venous return to the heart.
Adrenergic alpha-Agonists↗
Neurogenic histaminergic vasodilation in canine skeletal muscle: mediation by alpha 2-adrenoceptor stimulation.
This study examines the neurogenic effect of alpha 2-adrenoceptor stimulation on skeletal muscle vascular resistance and its relation to the level of background sympathetic activity. The isolated, separately perfused, neurally intact canine gracilis muscle preparation was used since it permits deliberate and quantifiable alterations in background sympathetic activity, as measured by skeletal muscle vascular resistance. Systemic intravenous UK-14304, a highly selective alpha 2-adrenoceptor agonist, produced a precipitous, neurogenic vasodilation that lowered vascular resistance below the subsequently denervated resistance, thus indicating that an active vasodilation was involved. The overall magnitude of the vasodilation was much greater in animals that had been hemorrhaged to elevate background sympathetic activity than in animals that had been transfused to lower background activity. The neurogenic vasodilation was unaffected by baroreceptor and cardiopulmonary receptor denervation and by prior cholinergic-receptor blockade of the gracilis muscle. Prior H1- and H2-histaminergic-receptor blockade, on the other hand, eliminated the active vasodilation but not a vasodilation down to the subsequently denervated resistance. Prior alpha 1-adrenoceptor blockade lowered resistance down to the subsequently denervated resistance and greatly attenuated the active vasodilation. The present study demonstrates that withdrawal of sympathetic activity by alpha 2-adrenoceptor stimulation produces an active vasodilation resulting from histamine release in skeletal muscle as well as a passive vasodilation resulting from lysis of peripheral vasoconstrictor tone.
Animals↗
Effect of changes in ventricular relaxation on early diastolic coronary blood flow in canine hearts.
Since the gradient between aortic pressure and left ventricular diastolic pressure is a major determinant of coronary blood flow, a change in left ventricular relaxation by its effect on early diastole could diminish early diastolic coronary flow. Two interventions that resulted in impaired left ventricular relaxation, hypothermia, and reperfusion following a left anterior descending coronary artery occlusion were studied to evaluate whether there were associated changes in coronary blood flow. With both interventions, there was a significant prolongation of left ventricular relaxation (p less than 0.01) accompanied by a significant decrease in early diastolic coronary blood flow (p less than 0.01). Verapamil did not have a significant effect on these hemodynamic changes during hypothermia. However, verapamil significantly blunted the effects of reperfusion following ischemia on ventricular relaxation (p less than 0.002) and early diastolic coronary blood flow (p less than 0.01). Thus, impaired left ventricular relaxation has an adverse impact on early diastolic coronary blood flow, which, under the condition of reperfusion following regional myocardial ischemia, can be alleviated with calcium channel blockade.
Animals↗
Detection of early necrosis in a canine model of low flow myocardial ischemia using 125I-antimyosin (Fab')2.
Low flow myocardial ischemia in the distribution of the left anterior descending coronary artery was established in 32 anesthetized dogs. The early development of irreversible myocardial injury was identified using 125I-antimyosin (Fab')2--a specific immunological marker of myocardial necrosis. The simultaneous injection of 131I-nonspecific (Fab')2 controlled for variables unrelated to specific antimyosin activity. It was also possible to calculate the relative uptake of 125I-antimyosin (Fab')2 in the ischemic area. In order to prevent recirculation of the (Fab')2, and to limit the time of exposure to the myocardium, the fragments were injected directly into the coronary circulation during diversion of the coronary sinus effluent. The antibody fragments were given either two, three or five hours after the onset of low flow in different groups of dogs and the animals were sacrificed 60 minutes later. Selective accumulation of 125I-antimyosin (Fab')2 in the ischemic area occurred between two and three hours after the onset of low flow ischemia indicating that necrosis was already established at this time. Macroautoradiographs of cross sections of the left ventricle and autoradiographs of microscopic sections of the ischemic myocardium independently confirmed selective accumulation of 125I-antimyosin (Fab')2 and hence necrosis, at three hours after the onset of low flow. In this study the use of 125I-antimyosin (Fab')2, in contrast to the use of histology, as a marker of necrosis avoided error due to sampling and also permitted the detection of cell death early during the ischemic process. The demonstration, within a narrow time frame, of early necrosis in this low flow preparation provides a potential model with which to evaluate agents for myocardial preservation in obstructive coronary disease.
Animals↗
Local and neurally mediated effects of sufentanil on canine skeletal muscle vascular resistance.
The present study examines both the local and neurally mediated effects of sufentanil, a new synthetic opioid, on the vascular resistance of the isolated, separately perfused canine gracilis muscle. Infusions (50 micrograms/min) of sufentanil into the gracilis arteries of nine denervated gracilis muscles did not produce a direct vascular effect. Because morphine has been previously shown to produce a central sympatholytic effect, the neural effect of sufentanil was examined in 12 innervated muscles under conditions of either low or high background sympathetic activity produced by either hemorrhage or transfusion of the dog. After i.v. sufentanil (20 micrograms/kg), all dogs experienced a rapid parallel fall in gracilis vascular resistance (GVR) and mean arterial pressure. The GVR decreased under conditions of high and low sympathetic activity. With low sympathetic tone, the GVR decreased from a control value of 24.1 +/- 4.4 S.E.M. to 6.6 +/- 0.8 resistance units (RU), a value below the subsequently denervated level (13.2 +/- 2.5 RU) (P less than .05). In hemorrhaged animals with elevated control sympathetic tone, resistance declined from 38.4 +/- 9.1 to 26.1 +/- 4.4 RU (P less than .05) but did not reach the denervated level (12.4 +/- 2.7 RU). Local intra-arterial pharmacologic blockade of the gracilis muscle was performed in animals with low sympathetic tone. Intra-arterial atropine did not effect the neurogenic vasodilatory response to sufentanil, whereas prazosin abolished it. Intra-arterial H1 and H2 receptor blockade prevented the decline of GVR secondary to sufentanil below the denervated level. Thus, vasodilation associated with sufentanil administration is mediated solely through neurogenic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic alpha-Antagonists↗
Defects in monocyte chemotaxis in patients with neoplastic disease.
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Chemotaxis, Leukocyte↗
Improvement in relaxation by nifedipine in hypoxic isometric cat papillary muscle.
Hypoxia has been demonstrated to cause impairment of myocardial relaxation. This impairment of relaxation is particularly pronounced during early reoxygenation. This study was undertaken in 24 isometric cat papillary muscles at 38 degrees C to determine if nifedipine can influence the impairment of relaxation produced during reoxygenation following hypoxia. A dose of nifedipine was chosen that produced only a minimal depression of peak systolic tension and no change in the half time to relaxation (RT 1/2) under well-oxygenated conditions. Thirty minutes of hypoxia were produced in 12 muscles, and systolic tension decreased by the same amount in muscles treated or not treated with nifedipine. During early hypoxia in the absence of nifedipine, RT1/2 was significantly prolonged (P less than 0.01) from 104 +/- 7 to 126 +/- 9 ms. After pretreatment with nifedipine, the change in RT1/2 with hypoxia was not significant. More striking was the near abolition of the marked impairment of relaxation seen during early reoxygenation (238 +/- 33 ms without nifedipine and 128 +/- 8 ms with nifedipine, P less than 0.01). These data establish that, although nifedipine only minimally attenuates the relaxation impairment early during hypoxia, this agent can substantially reduce the impairment of relaxation produced by early reoxygenation.
Animals↗
Acute alveolar hypoxia increases bronchopulmonary shunt flow in the dog.
To study the effects of alveolar hypoxia on canine bronchopulmonary shunt flow, a biventricular bypass preparation was employed. The preparation allowed a constant and sensitive measure of changes in pulmonary venous blood flow. In 16 of 18 dogs with intact bronchial arteries, alveolar hypoxia caused an increase in pulmonary venous return both under conditions of constant pulmonary arterial inflow and under conditions of no pulmonary arterial inflow, suggesting bronchopulmonary shunting. This effect was accompanied by systemic vasodilation despite vagotomy and ganglionic blockade, and was abolished by division of all bronchial vessels. Ibuprofen, 3 mg/kg, and indomethacin, 15 mg/kg, in dogs with intact bronchial vessels, abolished both the increase in pulmonary venous return and the systemic vasodilatation caused by hypoxia. Thus, alveolar hypoxia directly augments bronchopulmonary flow, most likely through release of one or more vasodilating prostaglandins.
Animals↗
Medical student research awards in cardiovascular science: the Stanley J. Sarnoff Endowment.
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Awards and Prizes↗
Effect of end-diastolic volume on the canine left ventricular ejection fraction.
Left ventricular ejection fraction is commonly used in the clinical assessment of ventricular function. However, the effect of changes in end-diastolic volume on ejection fraction is controversial. The present study examines the effect of changes in end-diastolic volume on ejection fraction in 26 anesthetized dogs on right heart bypass with controlled hemodynamics. At the end of each experiment, pressure-volume relationships were obtained in the potassium arrested heart following suturing of the mitral valve leaflets and clamping of the aortic root. This technique allowed determination of the end-diastolic volume from the end-diastolic pressure. Ejection fraction is highly dependent on end-diastolic volume and end-diastolic pressure at lower levels of end-diastolic volume and end-diastolic pressure. Ejection fraction increased from 30 +/- 1% (SEM) to 64 +/- 2% (p less than 0.001) when end-diastolic pressure was increased from 4 +/- 0.5 to 11 +/- 0.5 cm H2O. The corresponding end-diastolic volumes were 22 +/- 0.5 and 38 +/- 1 ml, respectively (p less than 0.01). Ejection fraction only increased from 64 +/- 2% to 71 +/- 1% (p less than 0.01) when end-diastolic pressure was increased from 11 +/- 0.5 to 18 +/- 1 cm H2O. The corresponding end-diastolic volumes were 38 +/- 1 and 50 +/- 1 ml (p less than 0.01), respectively. This dependence of ejection fraction on preload is present over a wide range of levels of aortic pressure. Similar directional changes in ejection fraction with preload were present after an adequate autonomic blockade, in the presence of either increased or decreased inotropic state and in the presence of an open or closed pericardium. Thus, the present study demonstrates that ejection fraction can be substantially altered by acute changes in end-diastolic volume. This factor should be taken into account when using ejection fraction for the clinical assessment of ventricular function.
Animals↗
Contribution of activation-inactivation dynamics to the impairment of relaxation in hypoxic cat papillary muscle.
Previous investigation of conventional isometric twitches of normothermic cat papillary muscle has shown that hypoxia prolongs relaxation, and this prolongation is actually accentuated during early reoxygenation. Our aim was to identify how hypoxia and reoxygenation affect the coupled processes of activation and inactivation that govern the time course of internally generated contractile tension (Ti). Activation and inactivation are modeled as first-order processes with rate constants ka and ki, respectively, and the overall isometric muscle as an underdamped second-order lag system driven by Ti. The analytical expression (To) for the externally recorded tension is dominated by two exponential terms incorporating ka and ki. Accurate least-squares fits of digitized twitches to To yielded estimates of ka and ki at 1- to 3-min intervals during control oxygenation, hypoxia, and early and late reoxygenation. Results follow. Compared with control, normothermic hypoxia prolonged activation [at 15 min ka decreased 61% from control, 35.5 +/- 6 (SE) s-1, P less than 0.05] and accelerated inactivation (at 15 min, ki increased 69% from control, 6.0 +/- 0.5 s-1, P less than 0.05). In early reoxygenation (1-3 min) activation remained impaired and inactivation returned to control levels (ki decreased 16% from control, NS). In late reoxygenation (15 min) both processes reverted to control. Thus inactivation kinetics can be dissociated from activation kinetics. Impaired relaxation in normothermic hypoxia is due to prolonged activation, whereas inactivation is actually accelerated. The further impairment of relaxation in early reoxygenation is due to rapid return of inactivation to control at a time when activation is still prolonged.
Animals↗
Effect of prostacyclin on vascular capacity in the dog.
Since the discovery of prostacyclin (PGI2) in 1976, there has been great interest in its vascular effects and potential clinical applications. High infusion rates of PGI2 markedly depress arterial blood pressure both in animal studies and in clinical trials. This fall in pressure may result entirely from a decrease in arterial resistance. However, it is possible that the administration of PGI2 may decrease ventricular filling due to an increase in vascular capacity. To investigate whether or not PGI2 affects vascular capacity, we infused PGI2 intraarterially at both 10 and 25 micrograms/min into 15 dogs on total cardiopulmonary bypass. These infusions were associated with a 25 +/- 3 mmHg decrease in arterial pressure and an increase in vascular capacity of 155 +/- 29 ml (SE, P less than 0.005). This increase in capacity was greater (P less than 0.02) than the increase of 23 +/- 42 ml resulting from infusions of nitroglycerin into eight dogs at 2 mg/min, which produced a decrease in arterial pressure of 23 +/- 4 mmHg, which was the maximal effect that could be achieved. Neither bilateral cervical vagotomy nor beta adrenergic blockade with propranolol significantly diminished the increase in vascular capacity associated with infusions of PGI2. The results from studies in four eviscerated dogs indicated that PGI2 acts on both splanchnic and extrasplanchnic capacity vasculature. To compare the direct effects of PGI2 with those of nitroglycerin and nitroprusside on venous tone, we used an isolated canine spleen preparation. Infusions of PGI2 (100 mcg/min) increased spleen weight in this preparation by 9.0 +/- 2.4% (n = 10, P less than 0.001); this increase was significantly greater than increases of 3.6 +/- 2.2% (P less than 0.001) and 3.5 +/- 2.3% (P less than 0.001) caused by high dose infusions of nitroglycerin (1 mg/min) and nitroprusside (400 micrograms/min), respectively. Thus, PGI2 substantially increases vascular capacity by a mechanism that appears to involve a direct action on vascular smooth muscle. Furthermore, these results suggest that PGI2 might be useful in clinical conditions in which an increase in vascular capacity is indicated.
Animals↗
Myocardial cell volume and coronary resistance during diminished coronary perfusion.
The present study was undertaken to determine whether diminished coronary blood flow without abrupt reperfusion results in myocardial cell swelling and, if so, whether the increment in tissue water is related to an increase in coronary vascular resistance. In 19 anesthetized open-chest dogs on right heart bypass with controlled coronary perfusion a decrease in coronary flow resulted in an increase in intracellular water and a progressive increase in coronary resistance. In 15 additional dogs, 180 min of ischemia produced by partially occluding the circumflex coronary artery resulted in significant increases in myocardial water content and progressive decreases in regional myocardial blood flow (microsphere technique). A significant correlation was found between the progressive decreases in myocardial flow and the increases in myocardial water (r = -0.82, P less than 0.001). In five experiments, hypertonic mannitol prevented water accumulation and progressive decreases in blood flow in the ischemic tissue. Thus myocardial ischemia produced by a decrease in antegrade coronary perfusion results in myocardial cell swelling and an associated progressive perfusion deficit.
Animals↗
[Effect of puerarin on regional myocardial blood flow and cardiac hemodynamics in dogs with acute myocardial ischemia].
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Acute Disease↗