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B Nuwayhid

Publications and source records attributed to B Nuwayhid.

36 records · Page 2Linked to original sources

Mechanisms of beat-to-beat variability in the heart rate of the neonatal lamb. I. Influence of the autonomic nervous system.

The contributions of the intrinsic, beta-adrenergic, and cholinergic systems to the mechanisms of beat-to-beat variability of the heart rate were investigated in chronically instrumented, unanesthetized newborn lambs from the first week to the eighth week of neonatal life. During this period of neonatal growth, the resting heart rate decreased spontaneously every week; the decrease was not related to alterations in the sympathetic and parasympathetic tones but rather to changes in the intrinsic mechanisms of heart rate control. Despite the weekly decrease in the resting heart rate of the neonatal lamb, the long and short-term beat-to-beat variabilities did not change significantly. This finding suggests an absence of a significant influence of the intrinsic mechanisms of heart rate control on the genesis of beat-to-beat variability. The results obtained with the various modes of adrenergic and cholinergic blockades and stimulation seem to indicate that the autonomic nervous system contributes significantly to the appearance of beat-to-beat variability. However, the influences of the adrenergic and cholinergic systems differ from week to week of neonatal growth and the patterns of changes are not the same for the long-term and short-term variabilities. The implication of these studies in terms of physiologic and hemodynamic significance of beat-to-beat variability in heart rate is discussed.

Aging↗

Mechanisms of beat-to-beat variability in the heart rate of the neonatal lamb. II. Effects of hypoxia.

The effects of acute hypoxia on the resting arterial pressure as well as on heart rate and its beat-to-beat variability were studied in chronically instrumented, unanesthetized newborn lambs at 2 to 8 weeks of neonatal life. Lung ventilation with a gas mixture containing 10% oxygen and 3% carbon dioxide decreased arterial blood PO2 by about 50% in all animals regardless of age without significantly altering blood pH and PCO2. This degree of hypoxia produced a mild pressor response, accompanied by a significant tachycardia; the pattern of these changes, however, differed somewhat according to neonatal growth. The impact of hypoxia on beat-to-beat variability of the neonatal heart rate also varied with age. When the lambs were 2 to 3 weeks old, both the long- and short-term variabilities decreased progressively during hypoxia and the decrement reached a maximum at 10 minutes of oxygen deprivation. As the lambs became older, however, there was some initial and transient increase in the long- and short-term variabilities in the early period of hypoxia but thereafter the changes were inconsistent. The significance of these observations is discussed in terms of our knowledge of the pathophysiologic alterations in the cardiovascular system produced by acute hypoxia.

Aging↗

Hemodynamic changes during pregnancy in the rabbit.

Blood volume (BV), plasma volume (PV), red cell volume (RCV), cardiac output (CO), and organ blood flows were measured in nonpregnant (Group I), 10 to 19 days' pregnant (Group II), and 20 to 30 days' pregnant (Group III) rabbits. BV, PV, and RCV increased throughout pregnancy, with maximum increase during the second third of gestation. CO peaked during the second third of gestation and then decreased. Mean arterial pressure and systemic vascular resistance decreased. Total reproductive blood flow increased throughout pregnancy but when calculated per unit of weight it did not change. Redistribution of blood flow within the reproductive organs occurred, with ovarian and placental flow per unit of weight increasing and myometrial flow/unit of weight decreasing. Splenic flow decreased significantly; liver flow decreased. The flow to the lungs and kidneys remained unchanged. The data suggested that major hemodynamic changes occur during the first two thirds of gestation and this period appears to test the competency of the maternal organism to adapt to the needs of pregnancy. The last one third of gestation is characterized by the fetoplacental unit interaction.

Animals↗

Effect of dopamine on hypotension induced by spinal anesthesia.

Chronically instrumented, near-term pregnant sheep were subjected to autonomic blockade with spinal anesthesia. Systemic arterial pressure, heart rate, and uterine blood flow decreased and uterine vascular resistance increased during the spinal blockade. Infusion of dopamine during the spinal hypotension corrected the disturbed circulatory parameters. These data provide evidence that: (1) the peripheral circulation of the near-term pregnant sheep is as sensitive as that of pregnant women to autonomic blockade, (2) the sensitivity is probably related to factors other than the changes in venous pressure in areas below the pelvis, and (3) dopamine represents a useful agent in the management of spinal hypotension.

Anesthesia, Spinal↗

Circulatory shock in pregnant sheep. IV. Fetal and neonatal circulatory responses to hypovolemia--influence of anesthesia.

Hemodynamic responses to hypovolemia were investigated in unanesthetized, unstressed fetal lambs and in acute fetal and neonatal preparations. The unstressed fetus tolerated twice the amount of blood loss of the acutely studied fetus or newborn lamb and with a lesser hypotension. Hemodynamic behavior of the newborn lamb and fetus anesthetized with pentobarbital during hypovolemia was markedly different from that of the fetus studied under spinal anesthesia or chronically. Besides tolerating greater blood loss, the unstressed fetus reversed the state of hypovolemic shock rapidly as contrasted to the stressed fetus which was unable to do so even with total blood reinfusion. All animals exhibited bradycardia in response to hypovolemia. The following conclusions were drawn: (a) cardiovascular response to hypovolemia in the perinatal period depends on the initial status of the animal, (b) the fetus tolerates a greater degree of blood loss than a newborn or adult animal, and (c) anesthesia and stress of surgery modify considerably circulatory behavior during blood loss.

Anesthesia↗

Systemic and uterine hemodynamic responses to dopamine in pregnant and nonpregnant sheep.

The systemic and uterine hemodynamic effects of dopamine were studied in nonpregnant and near-term pregnant, unanesthetized, chronically instrumented sheep. Dopamine was administered by constant intravenous infusion in doses ranging from 2 to 40 microgram per kilogram per minute. A hypertensive effect was consistently observed when doses greater than 5 microgram per kilogram per minute were given. The rise in pressure was accompanied by a rise in the systemic vascular resistance and an increase in the cardiac output; the increment in the latter was greater in the pregnant than in the nonpregnant animals. Uterine blood flow increased consistently despite some rise in uterine vascular resistance; uterine fraction of cardiac output either remained unchanged or increased slightly. Venomotor construction, reflected by a rise in central venous pressure, occurred at all dose levels. These hemodynamic properties of dopamine may be explained partly on the basis of its combined beta- and alpha-mimetic action, as well as through redistributions of flows and resistances among various regional vascular beds.

Animals↗

Control of the uteroplacental circulation in health and disease.

The various neurohumoral and intrinsic factors that control the uteroplacental hemodynamics in health and disease and in responses to physiologic and pharmacologic stimuli have been reviewed. The following conclusions may be derived: We still need improvement in our methodology of monitoring uterine blood flow. The present methods, which have some reliability, are not easily applicable to human subjects and even in animals their use presents problems of accuracy and sensitivity with which the investigator must become familiar. The marked and progressive increase in uterine blood flow that occurs during pregnancy is caused by complex factors, some of which are hormonal and hemodynamic in nature. The increased vascularity of the pregnant uterus and the opening of the arterioles during the process of formation of the intervillous space are important factors that facilitate the increase in uterine blood flow. The increment seems to be totally derived from the increment in the cardiac output that occurs during pregnancy. There seems to be no redistribution among the regional blood flows of the body. In the anesthetized condition the blood flow to the uterus depends largely on the perfusing pressure; the critical closing pressure seems to be around the 40 mm Hg level. This linear flow-pressure relationship does not, however, apply to the unanesthetized condition. A rise or fall in the perfusing pressure in the conscious state may be accompanied by an increase or decrease in the uterine blood flow, depending on the underlying mechanisms. Factors that lead to alpha-adrenergic stimulation produce an increase in uterine vascular resistance and a decrease in flow, irrespective of the status of the perfusing pressure. beta-adrenergic stimulation may increase uterine blood flow either through their vasodilating action or through their myometrial relaxing effects. Hypertensive diseases are most often accompanied by a decrease in uterine blood flow, whereas hypoxic states may decrease the flow even though the arterial pressure may not change significantly. It is extremely risky to extrapolate from information obtained in the anesthetized animal to the unanesthetized, conscious animal. Likewise, data obtained from normotensive conditions may not hold true for the hypertensive or hypotensive states. This is of particular relevance when one is dealing with the effects of pharmacologic agents that act on the cardiovascular system. Uterine contractions, whether induced through spontaneous or oxytocin-induced labor, produce a decrease in uterine blood flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Agonists↗

Cardiac output changes during neonatal growth.

Changes in resting cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR) during neonatal growth were studied in chronically instrumented lambs from the 1st to 5th wk of age; adult nonpregnant sheep values measured simultaneously were used as standard reference. Neonatal responses to autonomic agonists and antagonists were also investigated. Total CO increased linearly with neonatal growth, but decreased strikingly when expressed per weight unit; at 5 wk of age, CO/kg was still significantly higher than the adult value. SV also increased with neonatal growth but did not change when related to body weight; at 5 wk of age, SV/kg values were still higher than those of adult sheep. SVR changed reciprocally to CO. The decrease in CO/kg during neonatal growth paralleled the progressive decline in heart rate (HR). Beta receptor stimulation increased neonatal CO markedly and the increment was the same from the first through the fifth neonatal week. Beta blockade had insignificant effects, but cholinergic blockade produced moderate CO increases.

Aging↗

Cardiovascular reactivity of neonatal and adult sheep to autonomic stimuli during adrenergic depletion.

The cardiovascular responses of the neonatal and adult sheep to autonomic agonists and antagonists were studied in the resting state and following adrenergic neuronal depletion with reserpine. Both the neonates and adults showed similar supersensitivity of the effector system of the peripheral circulation to alpha adrenergic stimulation with catecholamines. In addition, the neonates exhibited supersensitivity of the myocardial effector system to beta-adrenergic stimulation. Unusual finding was a marked supersensitivity of the heart and peripheral circulation to cholinergic receptor blockade with atropine, the mechanisms of which are as yet unclear.

Acetylcholine↗

Development of neurohumoral control of fetal, neonatal, and adult cardiovascular functions.

Neurohumoral control of fetal, neonatal, and adult cardiovascular functions have been reviewed. Resting fetal heart rate remains fairly constant but neonatal heart rate declines progressively, reaching adult levels within six to eight weeks; systemic arterial pressure rises while pulmonary pressure falls to adult levels within the first week after birth. Sympathetic and parasympathetic control of circulatory functions matures at different rates during fetal and neonatal development; the sympathetic system becomes active earlier in fetal life than does the parasympathetic system. After birth, the parasympathetic tone of the resting heart rate rises to adult levels while adrenergic tone decreases. Despite changing autonomic activities, resting heart rate is set at given levels through alterations in intrinsic control. In the fetus, peripheral circulation is under neurohumoral tone of increasing magnitude; after birth, neurohumoral tone declines progressively, reaching levels comparable to those of adult nonpregnant sheep. Fetal cardiovascular response to neurotransmitters increases with age because of maturation of the effector system. The pulmonary bed responds primarily to acetylcholine whereas the systemic circulation responds to norepinephrine. After birth, the neonatal cardiovascular system becomes four to five times more sensitive to the action of neurotransmitters mainly because of closure of vascular shunts and elimination of umbilicoplacental circulation. In the neonate and adult, the pulmonary vascular bed loses its reactivity to neurotransmitters.

Animals↗

Continuous Fetal Scalp and Carotid Artery Oxygen Tension Monitoring in the Sheep.

Fetal scalp and carotid PO2 were recorded continuously by polargraphic oxygen electrodes at several levels of maternal oxygenation. The results were compared to measurements obtained by intermittent blood samples using the radiometer blood gas analyzer. There was a good correlation between the PO2 values measured by the implanted oxygen electrodes and by conventional analyses of blood samples collected anaerobically. Electrode measurements differed from the control radiometer values by a mean of +/- 1.2 mmHg; 2 SD= +/- 2.50. Scalp PO2 recordings were lower but paralleled the carotid recordings under varying degrees of maternally inspired O2 concentrations. Thus scalp PO2 levels reflect closely those in the central fetal circulation. Administration of 95% O2 to the mother resulted in a 27% increase of scalp PO2 and a 29% increase in the carotid artery PO2 when compare to room air.

Animals↗

Effects of estrogens on systemic and regional circulations in normal and renal hypertensive sheep.

Effects of estrogen administration on systemic and regional circulation were studied in normotensive and renal hypertensive, chronically instrumented nonpregnant and pregnant ewes. Arterial pressure, cardiac output, and uterine, renal, superior mesenteric, and iliac blood flows, as well as uterine oxygen transfer, were monitored before and after intravenous administration of Premarin or estradiol-17 beta. The results show that: (1) estrogen administration produces a marked decrease in uterine vascular resistance and increase in uterine blood flow and oxygen transfer, lasting for about 2 hours; (2) arterial pressure, cardiac output, and other regional blood flows were not affected by estrogens; (3) the magnitude of uterine vasodilatation produced by estrogens was greater in the hypertensive than in the normotensive animals; it was also greater in the nonpregnant than in the pregnant state; these findings indicate that the magnitude of uterine vasodilatation depends on the status of the uterine vascular resistance in the resting state; (4) blockade of the autonomic nervous system at various levels, as well as administration of a mild antihistaminic agent, failed to alter the magnitude of the estrogen-induced uterine vasodilatation. These results indicate that estrogens act directly on the uterine vascular bed and produce a redistribution of flows and resistances in the body; the precise sites of this redistribution are not as yet determined.

Animals↗

Renal hypertension and pregnancy in the sheep. I. behavior of uteroplacental vasomotor tone during mild hypertension.

The progressive changes in arterial pressure and uteroplacental hemodynamics were studied in 13 pregnant sheep from about the eightieth gestational day. All animals were followed to term. The results revealed a progressive increase in uteroplacental blood flow as the pregnancy progressed in the seven control animals. In six of the animals, mild hypertension was induced by unilateral renal artery constriction at about the one hundred fifteenth day. Following the induction of mild hypertension, there was a transient increase in uteroplacental vascular resistance and a reduction in uteroplacental blood flow. The arterial pressure remained significantly increased throughout the remainder of the gestation.

Animals↗

Development of autonomic control of fetal circulation.

Development of parasympathetic and sympathetic reflexes controlling heart rate, vascular pressures, and blood flows was investigated in fetal lambs weighing 300-5,800 g (65-165 days' gestation). Cardiovascular responses to veratridine injections, atrial stretching, bilateral cervical vagotomy, and cholinergic blockade with atropine were used to test parasympathetic activities. Responses to propranolol and phenoxybenzamine were used to test beta- and alpha-adrenergic activities. Autonomic ganglionic blockade and stimulation provided additional information on both cholinergic and adrenergic systems. Fetal responses to various tests were compared to those of the mother. Results show: a) little parasympathetic tone on resting heart rate and other circulatory functions exists prior to fetal maturity; b) despite the feeble resting tone, the parasympathetic system is capable of exerting significant control when stimulated in both premature and mature fetuses, the capability increases as fetus approaches term; c) alpha- and beta-adrenergic tone in control of resting heart rate and peripheral circulation exists in early fetal life and increases as the fetus reaches maturity, and both adrenergic receptors respond strongly to stimuli in immature, premature, and mature fetuses; d) in immature fetuses, veratridine does not elicit a vagally mediated reflex; instead, it produces a centrally mediated alpha- and beta-adrenergic stimulation; e) the fetal cardiovascular response to any given test is dampened by the existence of the various vascular shunts, the umbilicoplacental circulation and, possibly, by incomplete maturation of vasomotor tone.

Anesthetics↗

Systemic and pulmonary hemodynamic responses to adrenergic and cholinergic agonists during fetal development.

Systemic and pulmonary hemodynamic responses to adrenergic and cholinergic agonists were investigated in fetal lambs between 60 days and term gestation. The cardiovascular response to these agents increases with fetal age, and the increase is related to maturation of the effector system rather than the vascular receptors. The fetal pulmonary vascular bed and the ductus arteriosus are the primary components responding to acetylcholine; the systemic response is secondary to the occuring in the lung. Both fetal systemic and pulmonary vascular beds are under alpha-adrenergic control whereas the fetal heart is under beta-adrenergic control.

Acetylcholine↗

Maternal and fetal hemodynamic effects of diazoxide.

Effects of diazoxide on systemic and uterine hemodynamics as well as on fetal circulation and blood respiratory gases were investigated in chronically instrumented pregnant sheep. Diazoxide was administered intravenously either to the ewe or directly to the fetus in doses calculated on the basis of body weight. Transfer of drug across placenta was also investigated. Results showed that: a) when injected into the mother, there was consistent hypotensive effect with increased cardiac output and decreased systemic vascular resistance; uterine blood flow might not change or might decrease slightly with moderate hypotension; when maternal systemic arterial pressure fell to critical closing pressure level, uterine flow decreased significantly; but despite these maternal changes, the fetal circulatory functions were not significantly altered; b) when injected into the fetus in doses up to 15 mg/kg, diazoxide failed to alter fetal circulation appreciably; c) diazoxide crossed the placenta when injected intoeither mother or fetus according to a definite gradient; fetal levels were always lower than maternal levels because of rapid loss of the drug by the fetus; d) moderate maternal and fetal hyperglycemia occurred after drug administration.

Animals↗