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Biomedical subjects

E F Asher

Publications and source records attributed to E F Asher.

At least 19 recordsLinked to original sources

Pregnancy-induced alterations of uterine arteriolar reactivity in the rat: observations with a new in vivo microcirculatory preparation.

OBJECTIVE: The aim of this study was to compare reactivity of uterine arterioles in vivo between virgin and gravid rats. STUDY DESIGN: In anesthetized gravid and virgin rats circumferential arterioles were observed by videomicroscopy while vasoactive agonists were suffused over the uterus. Arteriolar diameter changes were compared. RESULTS: Resting and maximum diameters of circumferential arterioles were significantly larger in pregnant animals. Sensitivity to acetylcholine was greater in pregnant animals than in virgin animals (50% effective concentration, 7.1 +/- 0.17 negative log mol/L vs 6.1 +/- 0.32 negative log mol/L), whereas that to phenylephrine was less (50% effective concentration, 5.3 +/- 0.11 negative log mol/L vs 6.0 +/- 0.17 negative log mol/L). Angiotensin II-induced constriction was significantly reduced in pregnant rats only at lower concentrations. Serotonin significantly dilated arterioles in virgin rats (76% +/- 3% of maximum) but caused significant arteriolar constriction in pregnant animals (65% +/- 4% of maximum). CONCLUSION: The in vivo uterine microcirculatory preparation allows measurement of resistance vessels in the intact animal. Although these results differ from some previous reports, differences may be attributable to vessel location or to in vivo versus in vitro conditions.

Acetylcholine↗

Role of nitric oxide and cyclooxygenase products in controlling vascular tone in uterine microvessels of rats.

The importance of nitric oxide (NO) and dilator prostaglandins in uterine resistance arterioles was investigated. In pentobarbital anaesthetized rats at dioestrus-2, the uterine microcirculation in vivo was transilluminated by a fibreoptic probe and microvessels (circumferential arterioles) viewed by video microscopy. Arteriolar diameters were measured while increasing concentrations of acetylcholine (ACh), serotonin (5-HT), phenylephrine (PE), or angiotensin II (AII) were applied topically (suffused) over the uterus. Agonists were applied alone or with ibuprofen (IBU; cyclooxygenase inhibitor), N omega-nitro-L-arginine (L-NA; nitric oxide synthase inhibitor) or both. Circumferential arterioles were dilated by ACh and 5-HT (10(-8)-10(-4) mol l-1) and constricted by PE (10(-8)-10(-5) mol l-1) and AII (10(-11)-10(-7) mol l-1). Suffusion of L-NA or L-NA with ibuprofen (10(-4) mol l-1 each) abolished ACh-induced dilation; ibuprofen alone blocked dilation at higher ACh concentrations. Serotonin-induced relaxation was significantly attenuated by L-NA alone or in combination with ibuprofen. Vasoconstriction induced by PE was enhanced by L-NA alone and L-NA with ibuprofen, but ibuprofen alone had no effect. In contrast, AII-induced constriction was enhanced significantly by ibuprofen or L-NA and further enhanced when both ibuprofen and L-NA were present. These results suggest that ACh can release either nitric oxide (NO) or cyclooxygenase products to cause uterine arteriolar dilation and that 5-HT-induced uterine microvascular relaxation is mediated via NO only. They also suggest that PE-induced vasoconstriction is attenuated by the release of NO but not cyclooxygenase products and that constrictor responses evoked by AII are attenuated by both NO and dilator prostaglandin release. Thus, both nitric oxide and dilator prostaglandins are important in the control of uterine microvessels.

Acetylcholine↗

Human chorionic gonadotropin directly and indirectly alters uterine arteriolar diameters in cycling rats.

OBJECTIVE: Our purpose was to investigate whether uterine microvascular responses to human chorionic gonadotropin application depend on route of administration and estrous cycle day. STUDY DESIGN: One uterine horn was exteriorized in pentobarbital-anesthetized cycling and ovariectomized rats and superfused with Krebs solution Uterine arterioles (64 +/- 2.1 microns) were viewed by videomicroscopy. Diameters were measured during a 20-minute baseline period and for 60 minutes during human chorionic gonadotropin suffusion (20 IU/60 ml) or 60 minutes after intraperitoneal injection of 50 IU of human chorionic gonadotropin. Papaverine (100 mumol/L) suffusion maximally dilated the uterine arterioles (80 +/- 2.6 microns). RESULTS: Suffusion of human chorionic gonadotropin-dilated arterioles on diestrus-1 (122% +/- 2% baseline) and diestrus-2 (118% +/- 4% baseline) but constricted arterioles on proestrus (78% +/- 7% baseline). Intraperitoneal injection of human chorionic gonadotropin resulted in arteriolar constriction on diestrus-2 (76% +/- 5% baseline) and proestrus (82% +/- 3% baseline). Ovariectomy eliminated the effects of injected but not suffused human chorionic gonadotropin. All results are significant at p < 0.05. CONCLUSIONS: Results indicate estrous cycle day-dependent direct and indirect effects of human chorionic gonadotropin on the resistance of uterine arterioles.

Animals↗

A new technique for studying the uterine microvasculature in the rat.

OBJECTIVE: Our purpose was to develop a method for direct measurement of rat uterine microvessels and to test their viability. STUDY DESIGN: In anesthetized female Sprague-Dawley diestrus rats, one uterine hom was isolated from the body cavity with its nerve and blood supply intact. A small fiberoptic probe inserted into the lumen of the uterus served as a light source for transillumination of uterine vessels. Diameters of circumferential arterioles were observed while increasing concentrations of vasoactive agonists were suffused over the uterus. RESULTS: No significant diameter changes occurred in circumferential arterioles of the control group (100-minute suffusion of Krebs solution). Dilation with papaverine (100 mumol/L) demonstrated that vessels possessed basal tone. Circumferential arterioles showed concentration-dependent constriction to phenylephrine and angiotensin II and dilation to acetylcholine and serotonin. CONCLUSIONS: This uterine microcirculatory preparation provides a stable, reproducible model of a unique microcirculatory bed that responds to vasoactive agents in a manner similar to other microcirculatory beds.

Acetylcholine↗

Phrenic nerve injury following scalenectomy in a patient with thoracic outlet obstruction.

We present a case in which a patient with normal pulmonary reserve experienced orthopnea and hypoxia secondary to unilateral diaphragmatic paralysis following right scalenectomy. This operation was performed in an attempt to relieve neurovascular compromise at the thoracic outlet. To our knowledge, this association has not been previously described in the literature.

Dyspnea↗

Prostaglandin-related microvascular dilation in pentobarbital- and etomidate-anesthetized rats.

Etomidate is characterized by minimal systemic cardiovascular effects, but its effect on the microvasculature has not been assessed. We compared the microvasculature of etomidate-anesthetized animals to that of animals anesthetized with pentobarbital, since its effects on the microvasculature are known. Male Sprague-Dawley rats were anesthetized with etomidate or pentobarbital. The cremaster muscle was prepared for microscopic viewing, leaving the neural and vascular supply intact. Small arterioles were near their maximal diameters in etomidate-anesthetized rats, whereas the pentobarbital group had a large dilator capacity (maximal diameter-basal diameter/basal diameter). The effect on resting arteriolar diameters of endothelium-derived relaxing factor (EDRF) and prostaglandin synthesis inhibitors was tested. Dilator capacity was not affected by the EDRF inhibitor nitro-L-arginine, but it was significantly increased by mefenamic acid and ibuprofen in etomidate-anesthetized animals. To test whether dilator and constrictor mechanisms were normal, serotonin concentration-response curves were obtained in pentobarbital and etomidate-anesthetized animals with and without mefenamate or ibuprofen present. The dilation of small arterioles to serotonin in the etomidate groups with mefenamate or ibuprofen was not significantly different from that of the pentobarbital groups. Serotonin produced a comparable constriction of large arterioles in both anesthetic groups. The topical application of etomidate to the cremaster muscle did not affect arteriolar diameters. Thus, etomidate appears to trigger the release of dilator prostaglandins in striated muscle through a central or indirect mechanism.

Anesthesia, Intravenous↗

Halothane attenuates small arteriole vasodilation to serotonin (5-HT) in skeletal muscle.

Inhaled anesthetics may have an effect on the microcirculation through selective alteration of receptor-mediated control. Halothane was chosen because its actions in the microcirculation have been determined previously. Serotonin has received recent attention as a potential mediator of vascular changes in a number of disease states. We obtained concentration-response curves for serotonin-induced constriction of large arterioles and dilation of small arterioles (less than 60 microns diameter) in the cremaster muscle of halothane-anesthetized and decerebrate rats. Cremaster muscles were prepared for microscopic viewing, leaving the neural and vascular supply intact. Serotonin concentration-response curves were obtained before and after receptor antagonist application. Large arteriole constriction was not affected by halothane. Dilation of small arterioles was decreased in halothane-anesthetized animals but enhanced in the presence of methysergide, a nonspecific antagonist. These data indicate that halothane interferes with occupancy of 5-hydroxytryptamine receptors.

Animals↗

Urinary tract infections in the surgical patient.

Urinary tract infection (UTI) continues to be a common nosocomial infection. From a 2-year city-county hospital experience, 212 nosocomial UTI were identified in 153 patients from 3747 admissions. Mean age was 54 years; 102 were men. Foley catheterization was an associated factor in 129 patients (84%). UTI was caused by 40 different species of bacteria. In 28 infections (13%), the UTI was polymicrobial. Only nine patients had bacteremia. The bacteriology of the UTI depended on whether the patient had received systemic antibiotics previously during the hospitalization. Prior antibiotic administration increased the probability of Pseudomonas and Serratia as pathogens. Thus, patients that have had antibiotic therapy demonstrate a distribution of pathogens that are different from patients not receiving antibiotics, and a distribution different from the community-acquired UTI. Continued emphasis on the shorter duration and more judicious use of systemic antibiotics for both prophylaxis and therapy is warranted.

Adolescent↗

Effect of hemorrhagic shock on oxidative phosphorylation and blood flow in rabbit gastrointestinal mucosa.

The pathophysiologic mechanism responsible for ulceration of gastric fundus and corpus mucosa following hemorrhagic shock is not well defined. We examined the effect of hemorrhagic shock (25 ml blood/kg) and resuscitation (reinfusion of shed blood) on oxidative phosphorylation in different tissues of the rabbit to determine if differences in mitochondrial response to hemorrhagic shock and resuscitation contribute to the propensity of gastric fundus and corpus to necrose before other tissues. Blood flow was measured by using radioisotope-labeled microspheres to determine if changes in regional blood flow could be correlated with this propensity to ulcerate. The respiratory control index (RCI), an index of the integrity of mitochondrial function, was significantly increased in gastric antrum, liver, and kidney from the animals subjected to hemorrhagic shock and successful resuscitation when compared to control animals. In liver and kidney, these differences were largely due to increases in state 3 respirations. Duodenal and gastric corpus and fundus mitochondria showed no differences in RCI between bled and control groups. Blood flow data did not implicate ischemia as the mechanism responsible for the differential rate of ulceration after hemorrhage. The inability of fundus, corpus, and small-bowel mucosal mitochondria to respond to the stress of hemorrhagic shock and resuscitation in a manner similar to liver, kidney, and gastric antral mitochondria may place these tissues at greater risk to ulcerate. Further work is necessary to define whether this difference in mitochondrial response patterns represents a real increase in the maximal respiratory capacity of liver, kidney, and antrum after shock and resuscitation.

Animals↗

Experimental bacteremia and hepatic nutrient blood flow.

To study altered hepatic nutrient blood flow during the early phases of bacteremia, Sprague-Dawley rats (250-350 gm) underwent carotid cannulation; 24 hr later, they received an intravascular infusion of 2.5 X 10(8) Escherichia coli (LD70) over 45 min. Controls were anesthetized and cannulated only. Experimental and control animals then received a flow-dependent dose of indocyanine green (5 mg/kg) via the cannula, and arterial blood was sampled at 3, 4, 5, 6, 7, and 8 min after. Separate groups of animals were studied at 3 and 6 hr after bacteremia. The half-life (t1/2) of indocyanine green clearance was then determined at each time period, with t1/2 representing an estimation of total hepatic nutrient blood flow. Results indicated a prolonged t1/2 at both time periods in the bacteremic rats. Hepatic histology from plastic-embedded sections appeared to reveal fibrin, platelets, and leukocyte fragments within the sinusoids. From these data, we conclude that reduced nutrient blood flow occurs during experimental bacteremia prior to systemic changes of arterial pressure.

Animals↗

Postoperative pneumonia. Determinants of mortality.

Postoperative pneumonia continues to be a major cause of mortality on surgical services. The determinants that affect survival in patients in whom postoperative pneumonia develops are not clearly defined. We completed a retrospective analysis of 136 patients in whom postoperative pneumonia developed after they had major operative procedures between 1974 and 1980. These patients represented 1.3% of all operative cases, yet comprised 10% of the total 614 patients who died during the study period. The average age of the patients in whom pneumonia developed was 66 years. Significant determinants of death by chi 2 analysis included gram-negative pneumonitis, emergent operation, respirator-acquired pneumonia, postoperative peritonitis, and several factors that suggested that host defenses were overwhelmed (remote organ failure, positive blood cultures, or spread of infection to the second lung). We concluded that postoperative pneumonia is a disease of elderly patients and that survival depends on the ability of the surgeon to help the patient localize and resist the challenge presented by virulent gram-negative organisms.

Aged↗

Rural rotations for senior surgical residents. Influence on future practice location.

No information is available on factors that influence a surgeon's decision of where to practice. We surveyed all recent graduates of a surgical training residency program from a single institution to determine factors that influence this decision. An attempt was made to determine if a rural rotation during training ultimately influenced surgeons to locate their practices in rural areas. Ninety percent of 58 graduates responded: 44% entered a rural practice and 56% an urban and/or academic practice. A rural rotation during residency had been completed by 64% of the respondents. A significantly larger number of those who entered rural practice had completed a rural rotation than those who entered urban practice. Hometown size, level of debt, and other factors thought to be influential for other subpopulations of physicians were not found to be significant in this review.

Decision Making↗

Life after general surgery residency: subsequent practice patterns of chief residents.

No recent reports characterize the practice patterns of graduates of current general surgical residency programs. The University of Louisville Department of Surgery surveyed recent graduates of our program who were established in practice, to determine whether the training they had received had adequately prepared them for their subsequent positions. Ninety percent of our graduates responded to a questionnaire. More than 80% of residents still regularly performed general surgical procedures even though more than 38% had completed some additional fellowship training. More than 75% of our graduates were satisfied with their income. The vast majority were satisfied with their work load and their training. Although more data are needed to determine how practice patterns develop, no current evidence suggests that current training practices are inadequate or wasteful.

Fellowships and Scholarships↗

Endotoxin, cellular function, and nutrient blood flow.

To study the effects of endotoxemia on hepatic mitochondrial function and nutrient blood flow, rats were given intraperitoneal Escherichia coli endotoxin at a lethal dose for 90% mortality of group. Controls received only diluent. Five hours after the onset of endotoxemia, paired experimental and control animals had indocyanine green (ICG) clearance determined as the half-life (t1/2) at low (5 mg/kg) or high (15 mg/kg) doses. Low-dose ICG clearance represented hepatic nutrient blood flow; a Lineweaver-Burke plot of clearance rate v dose of administration provided extrapolation to an infinite dose and served as a sensitive indicator of hepatocellular function. Additional endotoxic rats were killed at five hours, liver and kidney mitochondria were isolated, and isolates were studied by the polarographic technique; the respiratory control index was determined as a sensitive indicator of efficient cellular oxygen metabolism with glutamate and succinate as substrates. Our data indicated that (1) uncoupling of the mitochondrial function is not identified during the early phase of endotoxemia, (2) reduced nutrient blood flow occurs during this early phase of endotoxemia, and (3) subsequent cellular abnormalities in endotoxemia may be secondary to ischemia and not direct cellular injury.

Animals↗

Alteration of arteriolar responses to serotonin by two intravenous anesthetics.

The effects of serotonin (5-HT) on the microvasculature of cremaster muscles were compared in decerebrate, ketamine- and pentobarbital-anesthetized rats. 5-HT-induced constriction of large distributing arterioles was enhanced in the ketamine- and pentobarbital-anesthetized rats. Precapillary arterioles of pentobarbital-anesthetized animals were more sensitive to 5-HT-induced dilation than either decerebrate or ketamine-anesthetized animals. The response of vessels to two 5-HT receptor antagonists (methysergide and LY53857) were unchanged by the anesthetics. Our findings suggest that both ketamine and pentobarbital enhance the microvascular response to 5-HT, but that these changes are not due to an alteration of receptor sensitivity.

Anesthetics↗