Biomedical subjects

M J Breslow

Publications and source records attributed to M J Breslow.

At least 55 records · Page 3Linked to original sources

PubMed1992

Negative chronotropic factor in patients with fungemia.

OBJECTIVE: To study the effect of serum from patients with fungemia and control patients on sinoatrial node function. DESIGN: Prospective, observational study. SETTING: Surgical ICU in a university hospital. PATIENTS: Fourteen patients with fungemia and 14 control patients. MEASUREMENTS AND MAIN RESULTS: Serum samples from all patients were assayed in an in vitro sinus node preparation. Serum samples from 11 (78%) of the 14 fungemic patients caused a decrease in sinus node activity, while serum samples from only one (7%) of 14 control patients caused slowing of the sinus node. CONCLUSIONS: Serum from many patients with fungemia causes slowing of an in vitro sinus node preparation. This in vitro finding may explain bradyarrhythmias seen clinically in the setting of fungemia.

Action Potentials↗

PubMed1992

The role of stress hormones in perioperative myocardial ischemia.

In this chapter I have tried to illustrate how trauma-induced changes in plasma catecholamines and other stress hormones can result in physiological alterations that may in turn increase the likelihood of developing myocardial ischemia. Data have been presented about potential mechanisms by which these hormones can lead to the development of ischemia, although additional work is required in this area. Among the strategies for modulating the stress response to surgery, the use of axial narcotics and perioperative administration of alpha 2-agonists can be easily instituted in most institutions. Additional studies are needed to determine whether these techniques reduce the incidence of perioperative ischemic complications. Because these interventions are labor intensive and therefore costly, further work is required to identify which subsets of patients may benefit from such aggressive management.

Coronary Disease↗

PubMed1992

Regulation of adrenal medullary and cortical blood flow.

Before 1986, little was known concerning regulation of blood flow to adrenal medulla and cortex. With the introduction of a radiolabeled microsphere methodology, which permitted independent measurement of blood flow to the two regions, it became apparent that medulla and cortex regulate blood flow independently and that both regions receive levels of blood flow considerably in excess of that required for nutrient delivery. It is likely that abundant blood flow serves to speed entry of adrenal secretory products into the systemic circulation. Coupling of blood flow with secretion is particularly apparent in medulla, where severalfold increases in blood flow occur during catecholamine secretion elicited by hemorrhage, hypoxia, and splanchnic nerve stimulation. Both catecholamine secretion and medullary vasodilation are neurally mediated. The two responses can be pharmacologically dissociated, suggesting possible direct innervation of adrenal vessels. However, morphological confirmation of vascular innervation is not available, and effects of released chromaffin cell products on adjacent vessels are also possible. In contrast to medulla, cortical secretory activity is not associated with altered blood flow. However, neural elements are found in close proximity to cortical vessels, and the cortical vasculature responds to changes in O2 tension and to a number of pharmacological agents. In addition, several studies indicate that cortical secretory activity can be modulated by changes in blood flow. The response of both vasculatures to pharmacological agents is, in many instances, different from responses observed in other vascular beds. These data indicate that the adrenal has evolved unique vasoregulatory mechanisms, either because vasoactive compounds are present in such high concentration, or because blood flow plays an important role in the secretory process.

Adrenal Cortex↗

PubMed1992

Muscarinic cholinergic receptors in canine adrenal gland.

Muscarinic cholinergic receptor stimulation has been reported to modulate adrenal catecholamine and steroid secretion and influence medullary vascular tone. The present study was undertaken to localize and characterize muscarinic cholinergic receptor binding sites in canine adrenal medulla and cortex. Binding studies using semipurified membranes demonstrated specific, saturable binding of L-[benzilic-4,4'-3H(N)]-quinuclidinyl benzilate ([3H]QNB) in medulla, with a dissociation constant (KD) equal to 152 pM and estimated maximal binding sites (Bmax) equal to 179 fmol/mg protein. Displacement of [3H]QNB by cholinergic agents in order of decreasing potency was atropine, pirenzepine, oxotremorine, pilocarpine, and carbamylcholine, suggesting the receptor was M1 subtype, similar to sympathetic ganglion muscarinic receptors. Autoradiographic imaging studies demonstrated highly specific, homogeneous binding throughout the medulla. No specific binding was found in adrenal cortex. These results suggest that muscarinic effects on blood flow may be neurally mediated, rather than the result of stimulation of vascular muscarinic receptors. In medulla, muscarinic receptors are evenly distributed and modulate catecholamine secretion in all cells rather than subpopulations of cells as in other species. Absence of [3H]QNB binding in cortex argues against muscarinic receptor modulation of cortical steroid secretion.

Adrenal Cortex↗

PubMed1991

Hyperadrenergic states.

OBJECTIVE: To review the physiologic and pathophysiologic hyperadrenergic states and the pharmacologic use of sympathomimetic agents. DATA SOURCES: Pharmacologic and physiologic studies in experimental animals and humans. DATA EXTRACTION/SYNTHESIS: Plasma catecholamines are increased in a variety of clinical situations. Following major injury, catecholamines act to support vital organ perfusion and mobilize fuel substrates. However, with surgical trauma and during acute medical illnesses, such as myocardial infarction, catecholamine-induced physiologic changes can interact with underlying disease processes to result in clinically significant complications. Exogenous catecholamines are used to treat a variety of medical conditions, including anaphylaxis and various shock states. Available sympathomimetic agents differ in their availability to stimulate different subpopulations of adrenergic receptors. These differences permit the astute clinician to achieve specific physiologic end-points. Finally, plasma catecholamines are increased in patients with pheochromocytoma. This latter condition provides insights into the long-term effects of catecholamine excess. CONCLUSIONS: Based on knowledge of the pharmacology of sympathomimetic agents and the physiologic consequences of adrenergic receptor stimulation, it is possible to prevent undesirable catecholamine effects and to utilize these agents to achieve desired therapeutic goals.

Adrenal Gland Neoplasms↗

PubMed1991

Effect of adrenal hypotension on elicited secretory activity in anesthetized dogs.

The objective of this study was to determine whether three- to fourfold increases in adrenal medullary blood flow (MQ), observed during catecholamine secretion induced by splanchnic nerve stimulation (NS), are necessary for a maximal secretory response. Eight pentobarbital-anesthetized adult male mongrel dogs (25-35 kg) were subjected to two episodes of NS-induced catecholamine secretion. To limit increases in MQ, one NS (20 Hz, 8 V, 1.5 ms) was performed under control conditions, the other was after reduction of adrenal perfusion pressure (PP). PP was 124.8 +/- 6.0 at control and was reduced to 23.0 +/- 1.0 mmHg by inflation of an aortic occluder located 3 in. above the adrenals. NS under control conditions increased ipsilateral MQ (measured using radiolabeled microspheres) from 181 +/- 39 to 1,336 +/- 199 ml.min-1.100 g-1 and adrenal epinephrine secretion from 184 +/- 128 to 11,445 +/- 5,216 ng.min-1.g medulla-1. Contralateral MQ and cortical blood flow were unaffected by NS. Reduction of PP decreased MQ to 32 +/- 6 ml.min-1.100 g-1 and adrenal cortical blood flow from 251 +/- 23 to 25 +/- 6 ml.min-1.100 g-1.PP reduction had no effect on either corticosteroid secretion or unstimulated epinephrine secretion. NS at reduced PP increased ipsilateral MQ to 146 +/- 27 ml.min-1.100 g-1 and epinephrine secretion to 13,935 +/- 5,175 ng.min-1.g medulla-1. These data indicate that epinephrine secretion is not altered when MQ is limited by reduction of PP and suggest that, at normal PP, increases in MQ during catecholamine secretion are not necessary for a maximal secretory response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

PubMed1991

Lack of coupling between adrenal cortical metabolic activity and blood flow in anesthetized dogs.

To determine whether adrenal O2 consumption and cortical blood flow (CBF) increase during stimulation of cortical secretory activity, exogenous adrenocorticotrophic hormone (ACTH) was infused at 0, 2, and 10 ng.kg-1.min-1 (groups 1, 2, and 3, respectively) into dexamethasone-pretreated, pentobarbital-fentanyl-anesthetized, ventilated dogs. ACTH levels of approximately 20, 100, and 500 pg/ml were obtained in groups 1, 2, and 3, respectively. Cortisol secretion increased after 20 min in groups 2 and 3 (from 0.016 +/- 0.004 to 2.25 +/- 1.36 and from 0.02 +/- 0.01 to 5.32 +/- 1.23 microgram.min-1.g cortex-1, respectively) while adenosine 3',5'-cyclic monophosphate (cAMP) secretion increased after 20 min only in group 3 (from 5.7 +/- 2.8 to 61.3 +/- 18.6 micrograms.min-1.g cortex-1). Whole adrenal gland O2 consumption increased after 20 min in group 3 animals (from 0.89 +/- 0.16 to 1.77 +/- 0.27 ml O2.min-1.100 g tissue-1) but not in the other two groups. CBF measured with radiolabeled microspheres was unaffected by ACTH infusion while O2 extraction increased from a baseline of 5.9 +/- 1.4 to 13.0 +/- 2.4% after 30 min in group 3. These data demonstrate that in anesthetized dogs increases in adrenal cortical secretory activity are associated with increases in O2 consumption, and this increase in O2 consumption is met by increasing O2 extraction, not by increasing cortical blood flow.

Adrenal Cortex↗

PubMed1991

Cholinergic regulation of adrenal medullary blood flow.

To determine the relative role of nicotinic and muscarinic mechanisms in splanchnic nerve stimulation (NS)-induced adrenal catecholamine secretion and medullary vasodilation, 12 pentobarbital-anesthetized dogs were subjected to three identical stimulations. The first NS was performed before drug administration and served as a control. The second NS was performed after administration of either the muscarinic antagonist, atropine 0.5 mg/kg (group 1), or the nicotinic antagonist, hexamethonium 20 mg/kg (group 2). The third NS was performed after administration of both drugs. NS in the absence of drug resulted in 4-fold and greater than 200-fold increases in medullary blood flow (Q, measured with radiolabeled microspheres) and catecholamine secretion (assayed by high-pressure liquid chromatography), respectively. Atropine, when administered alone (group 1), had no effect on these responses. Subsequent administration of hexamethonium to group 1 animals resulted in complete blockade of NS-induced changes in medullary Q and secretion. Hexamethonium alone (group 2) reduced the catecholamine response to NS by 95% but had no effect on the medullary Q response. Addition of atropine further attenuated the increase in catecholamine secretion induced by NS and completely blocked the medullary Q increase. These data suggest the presence of redundant mechanisms to increase medullary Q during NS. One mechanism likely involves neurally released acetylcholine-stimulating vascular muscarinic receptors, whereas the second requires either chromaffin cell degranulation or nicotinic ganglionic transmission.

Adrenal Medulla↗

PubMed1991

The role of anesthetic induction agents and neuromuscular blockade in the endotracheal intubation of trauma victims.

Management of extensive trauma often requires immediate tracheal intubation and mechanical ventilation. The role of anesthetic induction agents and neuromuscular blockade in the airway management of the trauma victim is disputed. To better define the role of these agents in the acute management of trauma, the adult trauma registry of The Johns Hopkins Hospital was reviewed to determine the frequency of use of these agents in acute airway management and to assess the effect of these agents on the incidence of complications. Ninety-seven patients were reviewed. Thirty-one patients were intubated because of cardiopulmonary arrest. Of the remaining 66 patients, oral intubation was initially attempted in 54. When drugs were used to facilitate intubation (n = 36), the success rate was 92 per cent on the first attempt, and 100 per cent on the second attempt. When drugs were not used (n = 18), 39 per cent could not be intubated (n = 7). Subsequent drug administration resulted in successful intubation of five of seven of these patients. Nasal intubation (no drugs) was only successful in 60 per cent of the patients (50 per cent on first attempt). Four patients required a cricothyrotomy. Two other patients vomited, and one patient aspirated. None of these patients received drugs prior to the first attempt at intubation. No hemodynamic or neurologic complications, related to relaxant or induction agent use, were observed. These findings suggest that oral intubation with drugs to facilitate airway management is most likely to result in successful intubation on the first attempt and that drug use in the trauma setting is safe.

Adult↗

PubMed1990

Pentoxifylline attenuates edema formation in proteolytic enzyme-induced lung injury.

Ex vivo canine lung lobes were exposed to a pancreatic proteolytic enzyme (chymotrypsin) alone or chymotrypsin after pretreatment with a continuous infusion with pentoxifylline. The lobes exposed to chymotrypsin gained 133 g, while the pentoxifylline-treated lobes gained only 65 g (p less than .05) over the 3-h experimental period. These results suggest that pentoxifylline significantly attenuates the lung weight gain associated with chymotrypsin.

Airway Resistance↗

PubMed1990

Changes in adrenal oxygen consumption during catecholamine secretion in anesthetized dogs.

Prior attempts to study adrenal medullary O2 metabolism during catecholamine secretion have been unsuccessful because venous blood from medulla mixes with venous blood from the much larger cortex. To circumvent this problem, eight adult mongrel dogs were pretreated for 5-6 wk with the adrenocorticolytic agent 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDD). Prednisolone (5 mg/day) and fludrocortisone (0.1 mg.10 kg-1.day-1) were administered orally to prevent adrenocortical insufficiency. Animals were then anesthetized with pentobarbital sodium and subjected to splanchnic nerve stimulation (NS) at 20 and 4 Hz to elicit catecholamine secretion. NS at 20 Hz increased epinephrine secretion from 1.6 +/- 0.7 to 1,780 +/- 762 ng.min-1.g medulla-1 but had no effect on medullary O2 consumption. Medullary blood flow (MQ) increased from 216 +/- 63 to 1,522 +/- 182 ml.min-1.100 g-1, and O2 extraction decreased from 2.7 +/- 0.7 to 0.8 +/- 0.2%. NS at 4 Hz increased epinephrine secretion from 3.1 +/- 1.4 to 76 +/- 17 ng.min-1.g medulla-1 and MQ from 226 +/- 66 to 649 +/- 122 ml.min-1.100 g-1 but had no effect on adrenal O2 consumption or extraction. Cortical blood flow was 342 +/- 98 ml.min-1.100 g-1 at baseline and was unaffected by NS. Gross weight of cortex was reduced by 80% in o,p'-DDD-treated animals, and histological examination of glands from three animals showed only rare islands of glomerulosa cells remaining. These data suggest that increases in MQ during NS do not occur in response to changes in O2 consumption.

Adrenal Glands↗

PubMed1990

Failure of endotoxic shock to elicit superoxide anion production in pig brain.

Endotoxin shock in pigs alters cerebral blood flow regulation. This study sought 1) to evaluate global cerebral electrical function using somatosensory evoked potential and 2) to determine if superoxide anion free radical (O2-) is generated in brain following endotoxin infusion. Five female pigs received E. coli endotoxin (0.1 mg/kg i.v.) and supplemental fluid to maintain cardiac output at control levels. Somatosensory evoked potential was generated before and after endotoxin infusion, and nitroblue tetrazolium (NBT) precipitation in cranial windows was used to determine O2- production by brain. Following endotoxin infusion, mean arterial blood pressure, cerebral perfusion pressure, and systemic vascular resistance fell by 50% and cerebral oxygen extraction increased. The amplitude and the latency of somatosensory evoked potential performed 60 min after endotoxin were unchanged from that generated at control. No precipitation of NBT in cranial windows was observed, indicating that O2- was not generated. Since endotoxin shock did not alter cerebral electrical function and O2- was not generated by brain, we conclude that alterations in cerebral blood flow regulation observed in fluid-resuscitated endotoxic shock do not result from inadequate cerebral oxygen consumption, nor is the extracellular production of O2- involved in the pathogenesis of this disorder.

Animals↗

PubMed1989

Adrenergic receptors of adrenal medullary vasculature.

The present study evaluates possible effects of adrenal catecholamines, released by splanchnic nerve stimulation, on adrenal medullary blood flow (MQ) and adrenal catecholamine secretion (CS). Twelve pentobarbital-anesthetized mongrel dogs were subjected to three identical splanchnic nerve stimulations (5 V, 20 Hz, for 3 min) at 30-min intervals, and MQ (radiolabeled microsphere technique) and CS (high-performance liquid chromatography) were measured before and during each nerve stimulation. Animals were assigned to one of three groups and administered either saline, pindolol (1 and 4 mg/kg), or prazosin (1 and 4 mg/kg) before the second and third nerve stimulation, respectively. In the saline control group, each nerve stimulation resulted in similar increases in MQ and CS. Pindolol attenuated nerve stimulation-induced increases in MQ and CS by 50%, but had no effect on medullary catecholamine concentration. Prazosin augmented nerve stimulation-induced MQ, CS, and medullary catecholamine concentration by 35%. These data suggest that adrenal adrenergic receptors modulate elicited CS and mediate changes in adrenal medullary vascular tone.

Adrenal Medulla↗

PubMed1989

Regional adrenal blood flow during hypoxia in anesthetized, ventilated dogs.

The effect of hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH) on adrenal medullary (MQ) and cortical (CQ) blood flow (radiolabeled microsphere technique) was studied in pentobarbital sodium-anesthetized, mechanically ventilated dogs. Animals were exposed to 60 min of hypoxia (arterial O2 content 8 vol%) induced by adding either nitrogen (HH, n = 6) or carbon monoxide (COH, n = 6) to the inspired gas. Whole adrenal Q and CQ increased by 70 and 50%, respectively, with HH but were unchanged during COH. MQ, however, increased threefold during both HH and COH. HH and COH both increased arterial levels of epinephrine, corticosteroids, and adrenocorticotropic hormone (ACTH). To determine whether the increase in CQ during HH was because of HH-induced increases in mean arterial blood pressure (MAP, approximately 20 mmHg), an additional group of animals (n = 6) was exposed to HH but had MAP maintained at control levels using a pressurized-bottle system. MAP control did not alter the CQ response to HH. We conclude that MQ appears to be associated with medullary secretory activity during hypoxia and that HH and COH stimulate adrenal medullary secretion equally. In contrast, CQ increases only with HH, despite similar increases in ACTH and corticosteroid levels during HH and COH, suggesting that an alternative mechanism is responsible for increased cortical blood flow during HH.

Adrenal Cortex Hormones↗

PubMed1989

Adrenal blood flow and secretory relationships during hypoxia in anesthetized dogs.

To evaluate whether hypoxia-induced increases in adrenal cortical (CQ) and medullary (MQ) blood flow (radiolabeled microspheres) occur secondary to hypoxia-induced secretory activity, pentobarbital-anesthetized ventilated dogs were pretreated with dexamethasone (DEX) to prevent adrenocorticotropic hormone (ACTH) and corticosteroid secretory changes or underwent unilateral adrenal denervation to prevent adrenal catecholamine secretory responses. In nonsurgically stressed dogs, DEX completely prevented increases in ACTH or corticosteroid levels during reduction of arterial oxygen content to 8 vol% but had no effect on hypoxia-induced doubling of CQ. In dogs in which adrenal oxygen consumption (VO2) was measured, DEX reduced VO2 by 50% without altering CQ. Unilateral adrenal denervation prevented hypoxia-induced increases in adrenal catecholamine secretion and MQ but had no effect on the CQ response. These results suggest that hypoxia-induced medullary vasodilation is associated with adrenal catecholamine secretory activity but that increases in CQ occur independent of secretory activity and likely represent direct vascular effects of hypoxia.

Adrenal Glands↗

PubMed1988

Effect of naloxone and ibuprofen on organ blood flow during endotoxic shock in pig.

The effects of an opiate antagonist naloxone and a cyclooxygenase inhibitor ibuprofen on organ blood flow during endotoxic shock were evaluated in a fluid-resuscitated porcine endotoxic shock model. Radiolabeled microspheres were used to measure regional blood flow. Escherichia coli endotoxin (0.1 mg/kg), infused intravenously over 40 min, reduced mean arterial blood pressure to 50 mmHg and systemic vascular resistance to 57% of control without affecting cardiac output. Endotoxin reduced blood flow to cerebrum (to 49% of control), kidney (to 25% of control), spleen, and skeletal muscle, while blood flow to left ventricle, stomach, and small and large intestines were unaffected. Sixty minutes after endotoxin administration, animals were randomized to one of three groups. Group I animals were controls and received no drug, group II animals received ibuprofen (12.5 mg/kg iv), and group III animals received naloxone (2 mg/kg iv) 60 min after endotoxin. Ibuprofen increased mean arterial blood pressure to 80 mmHg and increased blood flow to both cerebrum (to 92% of control) and kidney (to 47% of control). Plasma levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha were increased 8- and 16-fold, respectively, after endotoxin, and both were decreased by ibuprofen. Naloxone increased mean arterial blood pressure to 62 mmHg but had no effect on regional blood flow or plasma cyclooxygenase metabolite levels. These data suggest that cyclooxygenase metabolites may contribute to decreased mean arterial blood pressure and reduced organ blood flow during endotoxic shock in the pig.

6-Ketoprostaglandin F1 alpha↗

PubMed1987

Effect of vasopressors on organ blood flow during endotoxin shock in pigs.

A volume-resuscitated porcine endotoxin shock model was used to evaluate the effect on organ blood flow of increasing systemic arterial blood pressure with vasopressors. Administration of 0.05-0.2 mg/kg of Escherichia coli endotoxin (E) reduced mean arterial blood pressure (MAP) to 50 mmHg, decreased systemic vascular resistance to 50% of control, and did not change cardiac output or heart rate. Blood flow to brain, kidney, spleen, and skeletal muscle was reduced during endotoxin shock, but blood flow to left ventricle, small and large intestine, and stomach remained at pre-endotoxin levels throughout the study period. Four groups of animals were used to evaluate the effect of vasopressor therapy. A control group received E and no vasopressor, whereas the other three groups received either norepinephrine, dopamine, or phenylephrine. Vasopressors were administered starting 60 min after E exposure, and the dose of each was titrated to increase MAP to 75 mmHg. Despite the increase in MAP, brain blood flow did not increase in any group. Norepinephrine alone increased blood flow to the left ventricle. Kidney, splanchnic, and skeletal muscle blood flow did not change with vasopressor administration. The dose of norepinephrine required to increase MAP by 20-25 mmHg during E shock was 30 times the dose required for a similar increase in MAP in animals not receiving E. We conclude that hypotension in the fluid resuscitated porcine E shock model is primarily the result of peripheral vasodilatation, that the vascular response to vasoconstrictors in this model is markedly attenuated following E administration, that blood pressure elevation with norepinephrine, dopamine, and phenylephrine neither decreases blood flow to any organ nor increases blood flow to organs with reduced flow, and that norepinephrine, dopamine, and phenylephrine affect regional blood flow similarly in this model.

Animals↗

PubMed1987

Neural control of adrenal medullary and cortical blood flow during hemorrhage.

Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, we compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz (n = 4 each group) for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. We conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension.

Adrenal Cortex↗