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Biomedical subjects

N S Assali

Publications and source records attributed to N S Assali.

At least 37 records · Page 2Linked to original sources
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1977

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↗
PubMed1977

Blood volume in pre-eclampsia: fantasy and reality.

A great deal has been stated recently about the importance of hypovolemia in pre-eclampsia and eclampsia from the point of view of pathogenesis and management. Some authors even believe that the so-called hypovolemia represents an etiologic factor and should be "corrected." In this paper, the hemodynamic factors that maintain the circulation in the normal nonpregnant and pregnant states are discussed. These factors are then used as a background for explaining the pathophysiologic abnormalities of the acute hypertensive disease of pregnancy. It is concluded that the slight decrease in blood volume observed in pre-eclampsia has no hemodynamic relevance; the blood volume is merely "fitting" a contracted vascular bed. The major abnormality resides in the constricted arteriolar system and not in the blood volume.

Blood Circulation↗
PubMed1977

Circulatory effects of magnesium sulfate in normotensive and renal hypertensive pregnant sheep.

We have studied the effects of magnesium sulfate (MgSO4) administration in chronically instrumented normotensive and hypertensive pregnant sheep. Animals of 90 to 144 days' gestation were divided in two groups; those with normotensive arterial pressure and those in which renovascular hypertension had been produced. Our results show that bolus injection of 2 or 4 Gm. of MgSO4 caused a transient decrease in systolic and diastolic pressure which returned to control values within 5 to 10 minutes. The continuous infusion of MgSO4 in doses of 2 or 4 Gm. per hour produced a slight increase in uteroplacental blood flow but did not alter the blood pressure. Heart rate showed a slight increase. Because MgSO4 produced no significant hemodynamic changes, we feel that: (1) its use in obstetrics must be based on its anticonvulsant action and (2) MgSO4 in either normotensive or hypertensive patients is not associated with impairment of uteroplacental blood flow.

Animals↗
PubMed1977

Action of histamine and H1 and H2 blockers on the cardiopulmonary circulation.

Systemic and pulmonary hemodynamic responses to histamine were investigated inchronically instrumented unanesthetized nonpregnant ewes. Histamine was administered intravenously and into the pulmonary artery. The effects of the same doses of histamine were assessed following H1 and H2 receptor blockade. The effects ocular changes were also monitored. Results indicate that intravenous histamine produces tachycardia, systemic hypotension, pulmonary hypertension, and reduced cardiac output. The pulmonary response could be modified significantly by pentobarbital anesthesia. When injected directly into the pulmonary artery histamine failed to elicit any circulatory response. Blockade of H1 and H2 receptors, as well as autonomic ganglia, resulted in a comparable attentuation of the histamine circulatory response. It is concluded that a) central hemodynamic responses do not seem to be mediated through specific H1 and H2 receptors; b) histamine-induced pulmonary vasoconstriction can be reversed by pentobarbital anesthesia, and c) the absence of circulatory response to intrapulmonary histamine administration suggests that whatever receptors that may exist in the pulmonary vascular bed are not necessary for the central hemodynamic effects.

Animals↗
PubMed1977

Development of neuroeffector mechanisms in the carotid artery of the fetal lamb.

A survey has been made of mechanisms associated with vascular adrenergic neuroeffector transmission in the lamb fetuses between 53 days and term gestation. The common carotid artery was isolated for studies of enzymic activities, uptake of norepinephrine (NE) and reactivity to vasoactive agents. The extra-neuronal NE uptake, monoamine oxidase and catechol-O-methyltransferase activities were present in the carotid artery of the youngest fetuses. The contractile responses to NE and serotonin and neuronal NE uptake preceded the response to adrenergic nerve stimulation during fetal growth. These results suggest that the mechanisms for adrenergic transmitter inactivation, transmitter action on vascular smooth muscle cells, and neuronal transmitter delivery develop in that sequence.

Animals↗
PubMed1977

Autonomic control of cardiovascular functions during neonatal development and in adult sheep.

We studied the autonomic control of resting heart rate of systemic and pulmonary vascular blood pressures (BP) in chronically instrumented neonatal lambs 1-8 weeks of age. The maximum response to ganglionic blockade and sympathetic and parasympathetic antagonists was taken as an index of the magnitude of the total neural, adrenergic, and cholinergic tones. The reactivity of the circulatory parameters to adrenergic and cholinergic agonists also was investigated. All findings were compared with those in adult nonpregnant sheep studied concomitantly and with data previously obtained from term fetal lambs. The results of our studies show: (1) resting heart rate declines spontaneously throughout the 8 weeks of neonatal life approaching that of adult sheep; (2) the progressive bradycardia is not related to changes in the parasympathetic or sympathetic tone; (3) resting systemic BP is under strong neurohumoral control during the first two to three weeks of neonatal life; the control decreases progressively, becoming similar to that of adult sheep; (4) resting pulmonary artery pressure of neonatal and adult sheep has no neurohumoral control; (5) the systemic BP response of the neonate to autonomic agonists is greater than that of the term fetus and is similar to that of the adult; (6) in neonatal and adult sheep, compared to the term fetus, the pressor response to norepinephrine is accompanied by a baroreceptor-mediated bradycardia, and acetylcholine-induced systemci hypotension is accompanied by a "paradoxical" tachycardia mediated through beta-adrenergic stimulation; (7) in contrast to our finding for the fetus, the pulmonary vascular pressure of neonatal and adult sheep is unresponsive to autonomic agonists.

Acetylcholine↗
PubMed1976

Action of histamine and its receptor blockers on uterine circulation in sheep.

Effects of iv and ia administration of histamine and its H1 and H2 blockers (diphenhydramine and metiamide) on systemic arterial pressure, heart rate, and uterine and iliac blood flows were investigated in unanesthetized, chronically instrumented nonpregnant ewes. Intravenous histamine produced tachycardia, hypotension, and decreased iliac and uterine blood flows. In contrast, ia injections produced a significant increase in blood flows in these vascular beds which was dose-dependent. Evidence is presented to show that some of the circulatory actions of histamine may be related to stimulation of H1 while others may be related to H2 receptors. The peripheral circulatory action produced by iv histamine is probably secondary to its effects on reducing cardiac output. The uterine and iliac vascular beds contain mostly H1 receptors since their response to histamine can be blocked almost totally by Benadryl and not by H2 antagonist metiamide.

Animals↗
PubMed1976

Uteroplacental hemodynamic response to antihypertensive drugs in hypertensive pregnant sheep.

The production of renal hypertension by single renal artery constriction in pregnant sheep decreases uteroplacental blood flow. This decrease in uteroplacental perfusion persits for 7-10 days and then returns to normal control levels despite the persistence of hypertension. During hypertension the uteroplacental vascular bed is dependent upon the elevated arterial pressure for perfusion. Therefore, a pharmacologic lowering of this perfusion pressure may reduce uteroplacental blood flow. Antihypertensive agents whose major effect is the lower vascular resistance will tend to reduce uteroplacental blood flow, while those agents which increase cardiac output in addition to lowering the vascular resistance, will tend to maintain or increase uterine blood flow. Of the specific agents tested, hydralazine, which has a positive inotropic and chronotropic effect on the heart, was the only one that consistently increased uteroplacental blood flow. Blockade of these beta-mimetic effects resulted in a fall in uterine blood flow as the perfusion pressure was reduced.

Animals↗
PubMed1976

Fetal and neonatal cardiopulmonary response to histamine.

Effects of intravenous histamine and its H1 receptor blocker (Benadryl) were investigated in near-term fetal and in newborn lambs. Fetuses were studied before and after closure of the ductus arteriosus. Newborn lambs were chronically instrumented and the same animal was tested periodically from 3 to 70 days old. The results show that a) in the fetus whose pulmonary vascular resistance is already high, histamine produces a profound pulmonary vasodilation; b) in contrast, in the neonate with reduced pulmonary vascular resistance, histamine produces pulmonary vasoconstriction similar to that of the adult; c) both responses can be attenuated by Benadryl indicating that they are mediated by the same receptor; d) in the fetus, histamine produces marked constriction of the ductus arteriosus which could be partly attributed to the pulmonary vasocilatation; and e) when neonatal pulmonary vascular resistance was raised by hypoxia, histamine elicited a biphasic response, part of which was blocked by Benadryl. These findings are discussed in terms of their possible role in cardiovascular and pulmonary changes that occur after birth.

Animals↗
PubMed1975

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↗
PubMed1975

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↗