Search PubMed⌕ Search

Biomedical subjects

M J Breslow

Publications and source records attributed to M J Breslow.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effect of hemocarboperfusion on organ blood flow and survival in porcine endotoxic shock.

OBJECTIVE: To evaluate the effects of hemocarboperfusion on hemodynamics, organ blood flow, and survival in endotoxin shock. DESIGN: Prospective, placebo-controlled, animal trial. SETTING: Research laboratory in a major university teaching hospital. SUBJECTS: Pentobarbital-anesthetized pigs. INTERVENTIONS: Twenty-eight pentobarbital-anesthetized pigs (18.5 to 22.3 kg) received 100 micrograms/kg of Escherichia coli endotoxin (lipopolysaccharide 0127) over 30 mins. Group 1 animals (n = 14) were controls and had blood diverted through an extracorporeal circuit without activated charcoal for 60 mins after lipopolysaccharide infusion. Group 2 animals (n = 14) underwent nonpulsatile hemocarboperfusion (activated charcoal SCN-1K). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, cardiac output, systemic vascular resistance, mean pulmonary arterial pressure, pulmonary vascular resistance, oxygen delivery, and regional blood flow (radiolabeled microsphere technique) were determined at baseline and every 30 mins for 150 mins. Results are presented as mean +/- SD. Parameters in the two groups were compared by two-way analysis of variance. A p < .05 was considered significant. The survival rate was ten (71%) of 14 animals in group 1 compared with 14 (100%) of 14 animals in group 2 (p < .05, Fisher's exact test). The mean cardiac output at the end of hemocarboperfusion was 1.6 +/- 0.6 L/min in group 1 compared with 3.0 +/- 0.9 L/min in group 2, and remained lower in group 1 animals throughout the experiment. Pulmonary arterial pressure and pulmonary vascular resistance were lower in the hemocarboperfusion-treated animals during and after hemocarboperfusion. Systemic vascular resistance increased by 70% after lipopolysaccharide infusion and returned to baseline values in the hemocarboperfusion group but remained increased in controls. Oxygen delivery was lower in group 1 at 90 and 150 mins (287 +/- 34 vs. 478 +/- 48 mL/min and 251 +/- 24 vs. 356 +/- 21 mL/min, respectively). Blood flow rates to the brain (38.5 +/- 7.5 vs. 27.1 +/- 5.4 mL/min/100 g), large intestine (26.6 +/- 1.1 vs. 17.7 +/- 2.5 mL/ min/100 g), and adrenal cortex (200 +/- 45 vs. 139 +/- 41 mL/min/100 g) were higher in the hemocarboperfusion group at the completion of carboperfusion but not at later time points. CONCLUSION: These data suggest that hemocarboperfusion may be of value in the treatment of septic shock.

Animals↗
PubMed1995

The catecholamine, cortisol, and hemodynamic responses to mild perioperative hypothermia. A randomized clinical trial.

BACKGROUND: Unintended hypothermia occurs frequently during surgery and may have adverse effects on the cardiovascular system. Although the mechanisms responsible for the cardiovascular manifestations of hypothermia are unclear, it is possible that they are sympathetically mediated. In this prospective study, relationships between body temperature, the neuroendocrine response, and hemodynamic changes in the perioperative period were examined. METHODS: Seventy-four elderly patients, undergoing abdominal, thoracic, or lower extremity vascular surgical procedures, were randomly assigned to either "routine care" (n = 37) or "forced-air warming" (n = 37) groups. Throughout the intraoperative and early postoperative periods, the routine care group received standard thermal care, and the forced-air warming group received forced-air skin-surface warming. Core temperature, forearm minus fingertip skin-surface temperature gradient, and plasma concentrations of epinephrine, norepinephrine, and cortisol were measured throughout the perioperative period, and the two groups were compared. In addition, heart rate and arterial blood pressure were compared between groups. RESULTS: The routine care and forced-air warming groups did not differ with regard to age, sex, type of surgical procedures, anesthetic techniques, or postoperative analgesia. Mean core temperature was lower in the routine care group on admission to the postanesthetic care unit (routine care, 35.3 +/- 0.1 degree C; forced-air warming, 36.7 +/- 0.1 degree C; P = 0.0001) and remained lower during the early postoperative period. Forearm minus fingertip skin-surface temperature gradient (an index of peripheral vasoconstriction) was greater in the routine care group in the early postoperative period. The mean norepinephrine concentration (pcg/ml) was greater in the routine care group immediately after surgery (480 +/- 70 vs. 330 +/- 30, P = 0.02) and at 60 min (530 +/- 50 vs. 340 +/- 30, P = 0.002) and 180 min (500 +/- 80 vs. 320 +/- 30, P = 0.004) postoperatively. Mean epinephrine concentrations were not significantly different between groups. Mean cortisol concentrations were increased in both groups during the early postoperative period (P < 0.01), but the differences between groups were not significant. Systolic, mean, and diastolic arterial blood pressures were significantly higher in the routine care group. CONCLUSIONS: Compared with patients in the forced-air warming group, patients receiving routine thermal care had lower core temperatures, a greater degree of peripheral vasoconstriction, higher norepinephrine concentrations, and higher arterial blood pressures in the early postoperative period. These findings suggest a possible mechanism for hypothermia-related cardiovascular morbidity in the perioperative period.

Aged↗
PubMed1995

Multivariate determinants of early postoperative oxygen consumption in elderly patients. Effects of shivering, body temperature, and gender.

BACKGROUND: Previous investigators have proposed that postoperative shivering may be poorly tolerated by patients with cardiopulmonary disease because of the associated significant increase in total-body oxygen consumption. However, the often-quoted 300-400% increase in oxygen consumption with shivering was derived from relatively few studies performed in a small number of younger persons specifically selected on the basis of clinically recognizable shivering. We hypothesized that the average elderly postoperative patient has a shivering response that is associated with a relatively small increase in total-body oxygen consumption. METHODS: One hundred eleven elderly patients (age > 60 yr) undergoing surgery were studied to assess the determinants of shivering and total-body oxygen consumption in the early postoperative period. Anesthetic technique, postoperative analgesia, and thermal management were controlled by protocol. The clinical variables associated with shivering and increased total-body oxygen consumption were determined by univariate and multivariate analyses. RESULTS: Mean total-body oxygen consumption in shivering patients was 38% greater than in nonshivering patients. Regardless of whether data from shivering patients were included in the analysis, oxygen consumption was directly proportional to mean body temperature. Despite similar core temperatures, men had a greater incidence of clinically recognizable shivering and greater total-body oxygen consumption than did women. CONCLUSIONS: The metabolic demands associated with postoperative shivering in elderly patients are less than those reported previously in younger persons. These findings suggest that if hypothermia predisposes to cardiovascular complications in the postoperative period, these complications are not likely to be mediated by shivering and increased metabolism.

Aged↗
PubMed1995

Catecholamine and cortisol responses to lower extremity revascularization: correlation with outcome variables. Perioperative Ischemia Randomized Anesthesia Trial Study Group.

OBJECTIVE: To determine whether catecholamine and cortisol secretory responses to surgery contribute to postoperative complications. DESIGN: Prospective, randomized, case series. SETTING: A university hospital operating suite and surgical intensive care unit. PATIENTS: Sixty patients undergoing lower extremity vascular surgery. INTERVENTIONS: Patients were randomized to receive either epidural anesthesia/epidural opiate analgesia (regional anesthesia) or general anesthesia/intravenous patient-controlled analgesia (general anesthesia). MEASUREMENTS AND MAIN RESULTS: Anesthesia was managed according to a prospectively designed protocol. Hemodynamic parameters and plasma catecholamine concentrations were determined at specific intraoperative and postoperative time points. Intraoperative and postoperative urine samples were collected and analyzed for free cortisol concentrations. Outcomes evaluated were cardiac (nonfatal myocardial infarction and cardiac death) and surgical (graft occlusion). Mean arterial pressure during emergence from anesthesia and in the early postoperative period correlated positively with plasma norepinephrine concentration (p < .01). In addition, plasma catecholamine concentrations were higher in patients with postoperative hypertension. Plasma norepinephrine concentrations at the time of emergence from anesthesia and postoperatively were also higher in patients requiring repeat surgery for graft revision, thrombectomy, or amputation (p < .05). Multivariate analysis indicated that the norepinephrine concentration at the time of emergence, but not type of anesthesia, correlated with reoperation for graft occlusion, suggesting that the previously reported beneficial effect of regional anesthesia may be due to modulation of the stress response. Myocardial infarction or cardiac death occurred in three patients. These patients had markedly increased catecholamine concentrations. CONCLUSIONS: The catecholamine response to lower extremity vascular surgery contributes to the development of postoperative hypertension and may also be important in the development of thrombotic complications.

Adult↗
PubMed1994

Atypical beta-adrenoceptor in bovine adrenal medulla.

Bovine adrenal medullary membranes were incubated with [125I]cyanopindolol to assess beta-adrenoceptor binding. Binding was saturable and specific; a single low affinity site (Kd = 750 pM) was identified. [125I]Cyanopindolol binding was displaced by micromolar concentrations of classic beta-adrenoceptor antagonists and by sodium-4-[-2-[2-hydroxy-2-(-3-chloro-phenyl) ethylamino] propyl] phenoxyacetate. These data are similar to reported binding of beta 3-adrenoceptors and may explain beta-adrenoceptor agonist modulation of chromaffin cell degranulation in this catecholamine rich environment.

Adrenal Medulla↗
PubMed1994

Selective anesthetic inhibition of brain nitric oxide synthase.

BACKGROUND: It has been postulated that nitric oxide (NO) is a neurotransmitter involved in consciousness, analgesia, and anesthesia. Halothane has been shown to attenuate NO-mediated cyclic guanosine monophosphate accumulation in neurons, and a variety of anesthetic agents attenuate endothelium-mediated vasodilation, suggesting an interaction of anesthetic agents and the NO-cyclic guanosine monophosphate pathway. However, the exact site of anesthetic inhibitory action in this multistep pathway is unclear. The current study examines effects of volatile and intravenous anesthetic agents on the enzyme nitric oxide synthase (NOS) in brain. METHODS: NOS activity was determined by in vitro conversion of [14C]arginine to [14C]citrulline. Wistar rats were decapitated and cerebellum quickly harvested and homogenized. Brain extracts were then examined for NOS activity in the absence and presence of the volatile anesthetics halothane and isoflurane, and the intravenous agents fentanyl, midazolam, ketamine, and pentobarbital. Dose-response curves of NOS activity versus anesthetic concentration were constructed. Effects of anesthetics on NOS activity were evaluated by analysis of variance. RESULTS: Control activities were 57.5 +/- 4.5 pmol.mg protein-1.min-1 in the volatile anesthetic experiments and 51.5 +/- 6.5 pmol.mg protein-1.min-1 in the intravenous anesthetic experiments. NOS activity was not affected by ketamine (< or = 1 x 10(-4) M), pentobarbital (< or = 5 x 10(-5) M), fentanyl (< or = 1 x 10(-5) M), and midazolam (< or = 1 x 10(-5) M). Halothane decreased NOS activity to 36.7 +/- 2.5 (64% of control, P < 0.01 from control), 23.8 +/- 4.3 (41%, P < 0.01 from control and < 0.05 from 0.5% halothane), 25.2 +/- 3.8 (44%, P < 0.01 from control and < 0.05 from 0.5% halothane), and 19.7 +/- 2.8 (34%, P < 0.01 from control and < 0.05 from 0.5% halothane) pmol.mg protein-1.min-1 at 0.5, 1.0, 2.0, and 3.0% vapor. Isoflurane decreased NOS activity to 48.9 +/- 6.1 (85% of control), 46.0 +/- 3.2 (80%, P < 0.05 from control), 40.3 +/- 5.1 (70%, P < 0.05 from control), and 34.2 +/- 4.0 (60%, P < 0.05 from control and 0.5% and 1.0% isoflurane) pmol.mg protein-1.min-1 at 0.5, 1.0, 1.5, 2.0% vapor, respectively. CONCLUSIONS: Volatile anesthetics inhibit brain NOS activity in an in vitro system, but the intravenous agents examined have no effect at clinically relevant concentrations. This inhibition suggests a protein-anesthetic interaction between halothane, isoflurane, and NOS. In contrast, intravenous agents appear to have no direct effect on NOS activity. Whether intravenous agents alter signal transduction or regulatory pathways that activate NOS is unknown.

Amino Acid Oxidoreductases↗
PubMed1994

Adrenal blood flow and secretory effects of adrenergic receptor stimulation.

To evaluate effects of adrenergic receptor stimulation on regional adrenal blood flow and secretion, pentobarbital-anesthetized dogs (n = 5-6/group) received the beta-agonist isoproterenol (group I), the alpha 1-agonist phenylephrine (group II), or the alpha 2-agonist dexmedetomidine (group III). Measurements of adrenal cortical (CQ) and medullary (MQ) blood flow (radiolabeled microspheres) and catecholamine secretion were made before and during agonist infusion. Isoproterenol increased catecholamine secretion but had no direct effect on MQ or CQ. In contrast, phenylephrine increased MQ and CQ four- and twofold, respectively. Dexmedetomidine had no effect on MQ or catecholamine secretion. To evaluate whether blood flow effects of phenylephrine were due to increases in mean arterial blood pressure (MAP) or related to activation of alpha 1-adrenergic receptors, two additional groups of animals received phenylephrine; group IV had MAP maintained at baseline by controlled hemorrhage into a pressurized bottle; group V received prazosin before phenylephrine. Prevention of MAP increase did not prevent the vasodilation response to phenylephrine, but it was completely blocked by prazosin. Canine adrenal homogenates incubated with the alpha 1-adrenoceptor ligand, 125I-labeled 2-[beta-(4-hydroxyphenyl)ethlaminomethyl]tetralone, demonstrated specific and saturable binding, supporting the presence of alpha 1-adrenergic receptors. We conclude that increases in MQ and CQ elicited by phenylephrine appear to be due to alpha 1-receptor stimulation. The mechanism responsible for this vasodilation is not known.

Adrenal Cortex↗
PubMed1993

Perioperative platelet reactivity and the effects of clonidine.

BACKGROUND: Increased postoperative platelet reactivity may contribute to arterial thrombotic complications following surgery. alpha 2 Agonists, which are being used increasingly to blunt the stress response of surgery, increase platelet aggregation in vitro. We compared perioperative changes in platelet reactivity in 21 patients receiving either clonidine or placebo. METHODS: Patients undergoing major abdominal surgery were randomized to receive oral and transdermal clonidine (n = 11) or placebo (n = 10). All patients received similar perioperative management, including preoperative sedation, general anesthesia without neuraxial opioids, or local anesthetics and postoperative patient-controlled intravenous morphine. Blood was obtained for measurement of clonidine level, fibrinogen concentration, platelet count, and platelet reactivity (impedance aggregometry and dense granule release) before induction and 24, 48, and 72 h postoperatively. RESULTS: Thirteen of the 21 patients had biopsy-proven cancer at surgery, 5 of 11 received clonidine and 8 of 10 received placebo (NS). Clonidine levels were therapeutic (1-2 ng/ml) throughout the study period. Clonidine administration had no effect on platelet count or platelet reactivity. Therefore, the groups were combined for further analysis. In this group (n = 21), compared to preoperative values, fibrinogen levels rose maximally (36%) at 72 h postoperatively and platelet counts decreased 22% at 48 h. Platelet reactivity (aggregation and degranulation) to collagen, adenosine diphosphate, arachidonic acid, and ristocetin, increased at 24, 48, and 72 h postoperatively. Thrombin-induced (supramaximal stimulus) dense granule release did not change from preoperative values. CONCLUSIONS: These data indicate that major abdominal surgery causes increased platelet reactivity postoperatively but does not effect maximal degranulation. This increased platelet reactivity occurs within 48 h of surgery, coinciding with the peak incidence of postoperative arterial thrombotic complications. Clonidine administration has no effect on surgically induced changes in platelet reactivity. In this surgical patient population, the use of clonidine should not increase the risk of platelet-induced perioperative arterial thrombosis.

Abdomen↗
PubMed1993

The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Perioperative Ischemia Randomized Anesthesia Trial Study Group.

BACKGROUND: The purpose of this clinical trial was to compare the effects of different anesthetic and analgesic regimens on hemostatic function and postoperative arterial thrombotic complications. METHODS: Ninety-five patients scheduled for elective lower extremity vascular reconstruction were randomized to receive either epidural anesthesia followed by epidural fentanyl (RA) or general anesthesia followed by intravenous morphine (GA). Intraoperative and postoperative care were controlled by protocol using predetermined limits for heart rate, blood pressure, and other monitoring criteria. Data collection included serial physical examinations, electrocardiograms, and cardiac isoenzymes to detect arterial thrombosis (defined as unstable angina, myocardial infarction, or vascular graft occlusion requiring reoperation). Fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer levels were measured preoperatively and at 24 and 72 h postoperatively. RESULTS: Preoperative fibrinogen levels were similar in both groups, remained unchanged after 24 h, and increased equally (45%) in the first 72 h postoperatively. PAI-1 levels in the GA group increased from 13.6 +/- 2.1 activity units (AU)/ml to 20.2 +/- 2.6 AU/ml at 24 h and returned to baseline at 72 h. In contrast, PAI-1 levels in the RA group remained unchanged over time. Twenty-two of 95 patients (23%) had postoperative arterial thrombosis, 17 of whom had received GA and 5 of whom, RA. Preoperative PAI-1 levels were higher in patients who developed postoperative arterial thrombosis (20.5 +/- 3.6 AU/ml vs. 11.2 +/- 1.4 AU/ml). Multiple logistic regression analysis indicated that GA and preoperative PAI-1 levels were predictive of postoperative arterial thrombotic complications. CONCLUSIONS: Impaired fibrinolysis may be related causally to postoperative arterial thrombosis. Because RA combined with epidural fentanyl analgesia appears to prevent postoperative inhibition of fibrinolysis, this form of perioperative management may decrease the risk of arterial thrombotic complications in patients undergoing lower extremity revascularization.

Aged↗
PubMed1993

Determinants of catecholamine and cortisol responses to lower extremity revascularization. The PIRAT Study Group.

BACKGROUND: Surgical trauma elicits diffuse changes in hormonal secretion and autonomic nervous system activity. Despite studies demonstrating modulation of the stress response by different anesthetic/analgesic regimens, little is known regarding the determinants of catecholamine and cortisol responses to surgery. METHODS: Plasma catecholamines and cortisol secretion data were obtained from 60 patients undergoing lower extremity revascularization. Patients were randomized to receive either general anesthesia combined with patient-controlled intravenous morphine (GA) or epidural anesthesia combined with epidural fentanyl analgesia (RA). All aspects of intra- and postoperative clinical care were defined by written protocol. Plasma catecholamines were measured before induction, intraoperatively, and for the first 18 h postoperatively (by HPLC). Urine cortisol was measured intra- and postoperatively using RIA. Data were evaluated using univariate and multivariate analyses to evaluate demographic and perioperative variables as determinants of stress hormone secretion. RESULTS: Plasma catecholamines increased during skin closure in the GA group, and remained higher relative to the RA group in the postoperative period. Multivariate analysis indicated that age and anesthetic regimen predicted increases in catecholamines during skin closure (P < 0.005), although duration of surgery, blood loss, and body temperature were not correlated. Early postoperative norepinephrine concentrations were correlated with pain score and duration of surgery (P < 0.004), but not with anesthetic management, blood loss, or body temperature. All postoperative norepinephrine levels were highly correlated (r = 0.7) with norepinephrine levels during skin closure. Cortisol excretion was higher postoperatively than intraoperatively. No patient or perioperative variable predicted cortisol excretion, and cortisol excretion was not correlated with catecholamine levels at any time. CONCLUSIONS: These data indicate that patient factors, such as age and inherent sympathetic responsivity, are important determinants of the catecholamine response to surgery. Modulation of the norepinephrine response by regional anesthesia/analgesia appears to be related, in part, to superior analgesia. The lack of correlation between catecholamine and cortisol secretion indicates that the stress response may consist of discrete systems responding to different stimuli.

Adult↗
PubMed1993

Nitric oxide as a regulator of adrenal blood flow.

To determine whether nitric oxide (NO) is involved in adrenal medullary vasodilation during splanchnic nerve stimulation (NS)-induced catecholamine secretion, blood flow (Q) and secretory responses were measured in pentobarbital-anesthetized dogs before and after administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). L-NAME (40 mg/kg iv over 5 min, followed by 40 mg.kg-1.h-1) reduced NO synthase activity of medullary and cortical homogenates from 5.2 +/- 0.3 to 0.7 +/- 0.1 pmol.min-1.mg protein-1 and from 1.2 +/- 0.2 pmol.min-1.mg protein-1 to undetectable levels, respectively. L-NAME reduced resting medullary and cortical Q by 42 and 60%, respectively. NS before L-NAME increased medullary Q from 181 +/- 16 to 937 +/- 159 ml.min-1.100 g-1 and epinephrine secretion from 1.9 +/- 0.8 to 781 +/- 331 ng/min. NS after L-NAME had no effect on medullary Q (103 +/- 14 vs. 188 +/- 34 ml.min-1.100 g-1), while epinephrine secretion increased to the same extent as in control animals (1.9 +/- 0.7 vs. 576 +/- 250 ng/min). L-NAME also unmasked NS-induced cortical vasoconstriction; cortical Q decreased from 96 +/- 8 to 50 +/- 5 ml.min-1.100 g-1. Administration of hexamethonium (30 mg/kg iv), a nicotinic receptor antagonist, reduced NS-induced epinephrine secretion by 90%. These data suggest independent neural control of medullary Q and catecholamine secretion, the former by NO and the latter by acetylcholine.

Adrenal Glands↗
PubMed1993

Effect of acetylcholine infusion on adrenal vasculature and catecholamine secretion.

To evaluate effects of cholinergic receptor stimulation on regional adrenal blood flow (Q, radiolabeled microspheres) and catecholamine secretion, acetylcholine (ACh) was infused into pentobarbital-anesthetized, ventilated dogs. Unilateral adrenal denervation and placement of lumboadrenal catheters preceded intra-aortic infusion of 1) ACh alone (n = 6), 2) ACh plus hexamethonium (Hex) 20 mg/kg (n = 6), or 3) ACh plus atropine (Atr) (0.5 mg/kg) and Hex. ACh alone and in combination with Hex elicited similar dose-related (2, 20, and 100 mumol/min) increases in catecholamine secretion (181 +/- 61 to 1,055 +/- 229, 31,644 +/- 9,411, and 179,181 +/- 69,659 ng.min-1 x g medulla-1), whereas Hex and Atr together inhibited ACh-induced secretion by 95%. ACh caused marked medullary vasodilation (0.71 +/- 0.05 to 0.14 +/- 0.03 mmHg.ml-1 x min.100 g) in all three groups. To determine whether medullary vasodilation was due to incomplete muscarinic blockade, Hex-pretreated animals (n = 4) received ACh (100 mumol/min) and three increasing doses of Atr (0.5, 5, and 25 mg/kg). Catecholamine secretion was inhibited by all doses of Atr; however, vasodilation was blocked only by the two higher doses of Atr. These data suggest possible different mechanisms of muscarinic receptor-mediated catecholamine secretion and vasodilation.

Acetylcholine↗
PubMed1993

Substance abuse-related admissions to adult intensive care.

The frequency of adult surgical and medical intensive care unit (ICU) admissions related to substance abuse was determined at a large community, trauma, and tertiary referral hospital. Of 435 ICU admissions, 14 percent (95 percent confidence interval [CI], 5 to 23 percent) were tobacco related generating 16 percent of costs, 9 percent (95 percent CI, 0 to 18 percent) were alcohol related generating 13 percent of costs, and 5 percent (95 percent CI, 0 to 14 percent) were illicit drug related generating 10 percent of costs. In all, 28 percent (95 percent CI, 20 to 36 percent) of ICU admissions generating 39 percent of costs were substance abuse related. Substance abuse-related admissions were significantly longer and more costly than admissions not related to substance abuse (4.2 days vs 2.8 days, p = 0.004; $9,610 vs $5,890, p = 0.001). Frequency of substance abuse-related admission was linked with the patient's insurance status (Medicare, private insurance, uninsured). In the uninsured group, 44 percent of admissions were substance abuse related (95 percent CI, 35 to 52 percent), significantly higher than in the private insurance and Medicare groups, and generating 61 percent of all ICU costs in the uninsured group. Large fractions of adult ICU admissions and costs are substance abuse related, particularly in uninsured patients.

Adult↗