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Biomedical subjects

E Lowenstein

Publications and source records attributed to E Lowenstein.

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

Direct vasomotor effects of isoflurane in subepicardial resistance vessels from collateral-dependent and normal coronary circulation of pigs.

BACKGROUND: The purpose of the current investigation was to determine and compare the direct effect of isoflurane on normal resistance coronary arteries and similarly sized coronary arteries in collateral-dependent (CD) circulation. A differential vasomotor effect of isoflurane might contribute to flow redistribution, either adverse or favorable, between normal and CD regions. METHODS: The authors used a swine model of chronic coronary occlusion. Six weeks after ameroid occluder placement around the left circumflex artery, the heart was removed. Myocardial blood flow, measured in vivo before the removal, was lower during rapid atrial pacing in the CD region than in the normally perfused region. These in vivo studies established the existence and location of CD circulation. Subepicardial microvessels, measuring approximately 100 microns, were dissected from both the CD region and the normal region. Either with or without preconstriction of the vessels with the thromboxane analogue U46619 1 microM, direct vasomotor effect of isoflurane was examined in vitro by video microscopy. In addition, vasomotor responses to endothelin-1, the endothelium-dependent dilator adenosine 5' diphosphate, and the endothelium-independent dilator sodium nitroprusside were compared between CD and normal resistance vessels. RESULTS: Isoflurane caused greater concentration-dependent constriction of the normal vessels than of the CD vessels (P < 0.05); this constrictive effect was masked by preconstriction of the vessels. Vasodilation of ADP was less in CD vessels than in normal vessels (P < 0.001), but vasodilation to sodium nitroprusside was not significantly different (P = 0.45). Vasoconstriction to endothelin-1 was greater in CD vessels than in normal vessels (P < 0.01). CONCLUSIONS: The vasoconstrictive effect of isoflurane normally observed in coronary resistance vessels is impaired in resistance vessels that supply a CD area. The basis of this may be related to endothelial dysfunction.

Anesthetics, Inhalation↗
PubMed1996

Next-generation informatics. A new picture of quality medicine.

It's up to the physician executive to make an informed choice when selecting a "next-generation" information system. Look for systems that truly integrate (not merely interface) managed care components, clinical capabilities, and other features in a model that mimics the workflow of an actual practice. Take the time to learn about the technology. Consider how a vendor's product will work at every point within your organization. Seven critical features that physician executives should consider in their decision-making are described.

Decision Making↗
PubMed1995

Isoflurane attenuates cAMP-mediated vasodilation in rat microvessels.

BACKGROUND: Endothelium-dependent vasodilation mediated by cGMP is known to be attenuated by the inhalational anesthetic isoflurane. The present study examines the effect of isoflurane on beta-adrenergic and cAMP-mediated vasodilation. METHODS AND RESULTS: Fifty-three subepicardial coronary arteries (diameter, 103 +/- 13 microns) from Wistar rats were studied in vitro in a pressurized (40 mm Hg), no-flow state with use of optical density video detection system. After preconstriction of vessels with the thromboxane A2 analogue U46619 10(-6) mol/L, concentration response curves to the nonselective beta-adrenergic agonist isoproterenol, the Gs protein activator sodium fluoride, the adenylate cyclase activator forskolin, the cAMP analogue 8-Br-cAMP, or the phosphodiesterase inhibitor RO20-1724 were obtained either in the presence of absence (control) of 2% isoflurane. Relaxations to all the agents tested were significantly reduced in the presence of isoflurane compared with controls. CONCLUSIONS: Isoflurane attenuates cAMP-mediated vasodilation. The impairment appears to be distal to adenylate cyclase and is not due to enhancement of cAMP phosphodiesterase.

Adrenergic beta-Agonists↗
PubMed1995

Spurious ST segment depression by automated ST segment analysis.

Perioperative myocardial ischemia has been shown to be predictive of adverse cardiac outcome [1]. One method of detecting intraoperative myocardial ischemia is automated ST segment monitoring [2]. The rationale behind automated ST monitoring is that the clinician will be promptly alerted to ischemic changes in the ECG. This may lead to earlier intervention and, perhaps, improved outcome [3]. We describe a case in which automated ST segment monitoring falsely signaled the presence of intraoperative ST segment depression. This event emphasizes the importance of confirming the validity of ST segment changes before instituting therapy.

Aged↗
PubMed1995

Oxygen-derived free radicals mediate isoflurane-induced vasoconstriction of rabbit coronary resistance arteries.

Isoflurane induces endothelium-dependent constriction of rabbit coronary resistance arteries in vitro. This effect is inhibited by the cyclooxygenase inhibitor indomethacin. To determine whether thromboxane or oxygen-derived free radicals, a byproduct in the cyclooxygenase pathway, mediate this effect, subepicardial coronary arterioles (103 +/- 21 mu) from New Zealand White rabbits were studied in vitro in a pressurized (40 mm Hg), no-flow state using videomicroscopy. The vessels were subjected to increasing concentrations of isoflurane, 0%-3%, in the presence of Dazmegrel (a specific inhibitor of thromboxane synthesis; Pfizer Ltd., Sandwich, UK) or SOD-Mn (manganese superoxide dismutase, a scavenger of superoxide radicals) or mannitol (hydroxyl radical scavenger) 20 or 100 mM or in their absence (control). The control vessels showed a concentration-dependent constriction to isoflurane (P < 0.0001), with reduction in internal diameter of 11.4% +/- 3.5% at isoflurane 3%. This response was unaffected by Dazmegrel (P = 0.78), but was abolished by SOD-Mn (P < 0.01) or mannitol (P < 0.01). We conclude that isoflurane causes concentration-dependent constriction of rabbit coronary resistance arteries and that this effect is mediated by oxygen-derived free radicals.

Animals↗
PubMed1995

Propofol-associated dilation of rat distal coronary arteries is mediated by multiple substances, including endothelium-derived nitric oxide.

Previous in vitro studies on the effect of propofol on coronary arteries have shown variable results, ranging from constriction to no effect to dilation. Although most of these studies reported that the observed effect is endothelium-independent, propofol also releases nitric oxide from cultured porcine endothelial cells. The present study examines the direct effect of propofol in rat distal coronary arteries in vitro, especially in regard to endothelial dependence and involvement of the adenosine triphosphate (ATP)-sensitive potassium channels (KATP channels). Forty-three subepicardial arteries (size 91.1 +/- 15.8 microns) from Wistar rats were studied in vitro in a no-flow, pressurized (40 mm Hg) state, using an optical density video detection system. After preconstriction with the thromboxane analog U46619 1 microM, relaxation responses to increasing concentrations of propofol (10(-6)-10(-4) M) were measured after 1) endothelial denudation, 2) pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA), 3) pretreatment with the cyclooxygenase inhibitor indomethacin, 4) pretreatment with the KATP channel blocker glibenclamide, or 5) no intervention (control). Propofol produced a significant concentration-dependent vasodilation of the U46619-preconstricted coronary arteries. This effect was significantly attenuated by endothelial denudation, pretreatment with L-NNA, or indomethacin, but was not affected by glibenclamide. We conclude that propofol has a direct vasodilatory effect on distal coronary arteries in rats. This effect is primarily endothelium-dependent and is mediated by multiple substances, including nitric oxide (NO) and a vasodilatory prostanoid. The effect is not mediated by opening of the K(ATP) channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

Vasomotor responses of rat coronary arteries to isoflurane and halothane depend on preexposure tone and vessel size.

BACKGROUND: The authors previously reported that in rabbits, isoflurane exhibited a heterogeneous vasomotor effect, constricting small resistance coronary arteries and dilating larger conductance arteries. The novelty of isoflurane-induced constriction of small coronary arteries raised the question of whether the finding depended on the unique experimental setup or species used. The purpose of this study was to address these questions. Therefore, a second species was studied, namely rats, as well as a second volatile anesthetic, halothane. In addition, the dependence of the vasomotor effect on the preexisting tone of the vessels was examined. METHODS: Thirty-six large coronary arteries (262 +/- 23 microns) and 42 small coronary arteries (99 +/- 15 microns) from 31 Wistar rats were isolated. Each vessel was placed in a microvessel chamber and was (1) submaximally preconstricted with the thromboxane analog U46619; (2) submaximally predilated with sodium nitroprusside; or (3) neither preconstricted nor predilated. The vessel was then subjected to increasing concentrations of either isoflurane or halothane, 0-3%. Changes in inner diameter were monitored and recorded with optical density video detection system. RESULTS: Isoflurane constricted predilated or untreated small coronary arteries, but had no effect on preconstricted small arteries. Isoflurane dilated large coronary arteries, with the preconstricted vessels dilating the most. In contrast, halothane dilated both the small and large coronary arteries to a similar extent. Preconstricted vessels dilated more to halothane than vessels with no added tone. CONCLUSIONS: Whereas isoflurane has a heterogeneous vasomotor effect in rat coronary arteries, constricting the small vessels and dilating the large ones, halothane dilates both the small and large arteries. The vasoconstriction effect was most evident in vessels with no added tone, whereas the vasodilatory effect was most significant in preconstricted vessels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2).

Abnormalities due to chromosomal aberration or point mutation in gene products of growth factor receptors or in ras gene products, which lie on the same signaling pathway, can cause disease in animals and humans. Thus, it can be important to determine chromosomal map positions of genes encoding "adapter" proteins, which are involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as ras, because adaptor protein genes could also, logically, serve as targets of mutation, rearrangement, or other aberration in disease. Therefore, DNAs from panels of rodent-human hybrids carrying defined complements of human chromosomes were assayed for the presence of the cognate genes for NCK, SHC, and GRB2, three SH2 or SH2/SH3 (Src homology 2 and 3) domain-containing adapter proteins. Additionally, NCK and SHC genes were more narrowly localized by chromosomal in situ hybridization. The NCK locus is at chromosome region 3q21, a region involved in neoplasia-associated changes; the SHC cognate locus, SHC1, is at 1q21, and the GRB2 locus is at 17q22-qter telomeric to the HOXB and NGFR loci. Both SHC1 and GRB2 are in chromosome regions that may be duplicated in some tumor types.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Heterogeneous vasomotor responses of rabbit coronary microvessels to isoflurane.

BACKGROUND: Previous in vitro studies on the mechanism of isoflurane-elicited vasodilation have examined conductance arteries and reported conflicting data on whether the vasomotor response is mediated through the release of endothelium-derived nitric oxide. The current study was undertaken to define the effect of isoflurane on both resistance and conductance coronary arteries in rabbits and to elucidate the mechanism of the effect. METHODS: Rabbit coronary arteries of varying sizes were dissected and each placed in a microvessel chamber. The arteries were studied in a pressurized (40 mmHg), no-flow state and were exposed to increasing concentrations of isoflurane, 0-3%, by an in-line bubble-through vaporizer. The vessel lumen diameter was monitored using an optical density video detection system. Selected experiments were performed on microvessels after preincubation with indomethacin, NG-monomethyl-L-arginine, or methylene blue or after endothelial denudation. RESULTS: Isoflurane caused a dose-dependent constriction of small rabbit coronary arteries (internal diameter of 139 +/- 34 mu, mean +/- SD), whereas it caused dilation of large coronary arteries (371 +/- 54 mu). The vasoconstriction of the small coronary arteries by isoflurane was abolished by endothelial denudation or after preincubation with indomethacin. The vasodilation of the large vessels by isoflurane was inhibited by endothelial denudation or after preincubation with NG-mono-methyl-L-arginine, methylene blue, or indomethacin. CONCLUSIONS: Our data suggest that vessel size is a determinant of the vasomotor response to isoflurane. Exposure to isoflurane produces vasodilation of conductance coronary arteries, whereas it is associated with vasoconstriction of resistance coronary microvessels. The latter appears to be endothelium-dependent and mediated by cyclooxygenase product(s), whereas the former, also endothelium-dependent, is mediated by both product(s) of cyclooxygenase and endothelium-derived nitric oxide.

Animals↗
PubMed1993

The function of GRB2 in linking the insulin receptor to Ras signaling pathways.

Insulin-induced activation of extracellular signal-regulated kinases [ERKs, also known as mitogen-activated protein (MAP) kinases] is mediated by Ras. Insulin activates Ras primarily by increasing the rate of guanine nucleotide-releasing activity. Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. Moreover, a dominant negative form of Ras (with Ser17 substituted with Asn) blocked insulin-induced activation of ERKs in cells that overexpressed GRB2. GRB2 overexpression led to increased formation of a complex between the guanine nucleotide-releasing factor Sos (the product of the mammalian homolog of son of sevenless gene) and GRB2. In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Implications of triiodothyronine administration before cardiac and noncardiac operations.

Before the potential for the use of a revolutionary new strategy such as administration of triiodothyronine before or during cardiac or noncardiac operations can be evaluated, previous aspects of anesthetic management of patients with coronary artery disease must be considered. In the late 1970s, efforts were made to minimize myocardial oxygen consumption to improve postsurgical mortality. These consisted of attempts to limit myocardial oxygen demand (eg, keeping heart rate low, preventing hypertension, maintaining coronary perfusion pressure). Subsequently, clinical findings indicated that nonhemodynamic ischemia was common during anesthesia. A second era of anesthetic management of patients with coronary disease was aimed at preventing reduced myocardial oxygen supply because coronary vasomotion was found to be related to myocardial ischemia. Because myocardial ischemia is still associated with apparently well-managed anesthesia and operation, investigators are now looking for new avenues to prevent morbid perioperative ischemic events. Investigational agents including intravenous triiodothyronine may serve as cardioprotective agents in the future if they are proven to prevent ischemia or enhance efficiency of contraction without tissue injury in ischemic or postischemic myocardium.

Cardiac Surgical Procedures↗
PubMed1993

Clinical markers and clinical consequences of stunned myocardium.

Clinical markers must be identified to distinguish between stunned and acutely ischemic myocardial tissue, as well as to assess the viability of myocardium. Evaluation of electrocardiographic ST segment abnormalities can distinguish transmural oxygen deprivation from subendocardial oxygen declines, but stunned myocardium may have normal ST segments. Myocardial contrast echocardiography can estimate regional myocardial blood flow but ultrasound measurement of blood flow is not always able to discern stunned from nonviable myocardium. Change in extracellular pH has been used to study ischemia, but has not yet been shown to reflect differences between stunned and ischemic myocardium. A combination of clinical markers of flow, delivery, and oxygen consumption may be necessary in order to differentiate between stunned and ischemic regions. This distinction can have important therapeutic consequences because patients with acutely ischemic but viable myocardium may be ultimately harmed by inotropic drugs that increase myocardial oxygen demand. In contrast, inotropes may be indicated for stunned myocardial tissue. The determination of the reversibility of myocardial dysfunction can also impact on decisions to use mechanical cardiocirculatory support. Differentiation of stunned and ischemic myocardium might also streamline ICU assignments and lead to more effective use of high technology resources.

Cardiac Surgical Procedures↗
PubMed1991

Cloning of PI3 kinase-associated p85 utilizing a novel method for expression/cloning of target proteins for receptor tyrosine kinases.

A novel method has been developed to allow cloning of protein targets for receptors with tyrosine kinase activity. By utilizing the carboxy-terminal tail of EGF receptor (EGFR) as a probe to screen lambda gt11 expression libraries, several EGFR-binding proteins have been cloned; two have been analyzed and contain unique SH2 and SH3 domains. One gene (GRB-1) has been fully sequenced, is expressed in various tissues and cell lines, and has a molecular mass of 85 kd. Interestingly, GRB-1 encodes the human counterpart of the PI3 kinase-associated protein p85. Advantages of this technique include the ease of cloning tyrosine kinase receptor targets present at low levels and the ability to identify proteins that are related in their capacity to bind activated receptors but contain no significant DNA sequence homology. This method, termed CORT (for cloning of receptor targets), offers a general approach for the identification and cloning of various receptor targets.

Amino Acid Sequence↗
PubMed1991

Myocardial perfusion as assessed by thallium-201 scintigraphy during the discontinuation of mechanical ventilation in ventilator-dependent patients.

Patients who cannot be separated from mechanical ventilation (MV) after an episode of acute respiratory failure often have coexisting coronary artery disease. The authors hypothesized that increased left ventricular (LV) wall stress during periods of spontaneous ventilation (SV) could alter myocardial perfusion in these patients. Using thallium-201 (201TI) myocardial scintigraphy, the authors studied the occurrence of myocardial perfusion abnormalities during periods of SV in 15 MV-dependent patients (nine women, six men; aged 71 +/- 7 yr, mean +/- SD). Fourteen of these patients were studied once with 201TI myocardial scintigraphy during intermittent mechanical ventilation (IMV) and again on another day, after at least 10 min of SV through a T-piece. One patient was studied during SV only. Thirteen of 14 of the patients (93%) studied during MV had abnormal patterns of initial myocardial 201TI uptake, but only 1 patient demonstrated redistribution of 201TI on delayed images. The remainder of the abnormalities observed during MV were fixed defects. SV produced significant alterations of myocardial 201TI distribution or transient LV dilation, or both, in 7 of the 15 patients (47%). Four patients demonstrated new regional decreases of LV myocardial thallium concentration with redistribution of the isotope on delayed images. The patient studied only during SV also had myocardial 201TI defects with redistribution. Five patients (3 also having areas of 201TI redistribution) had transient LV dilation during SV.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗