Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery

Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 microM), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9-0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentration-dependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re-evaluated, since this substance may act as a partial agonist.     

Pulmonary vascular permeability after cardiopulmonary bypass and its relationship to oxidative stress

A straightforward quantitative method for gas chromatography-mass spectrometry determination of isosorbide 5-mononitrate (IS5MN) and its related impurities such as isosorbide (IS), isosorbide diacetate (ISDA) and isosorbide 2-acetate-5-nitrate (IS2A5N) in raw materials as well as in dosage formulations is developed. The recovery of these materials was found to be 100.4 +/- 2.4, 99.3 +/- 4.7, 97.8 +/- 5.2 and 100.1 +/- 3.1%, while the detection limits were 27.2, 1.26, 1.02 and 0.78 micrograms in dosage formulations for IS5MN, ISDA, IS2A5N, and IS, respectively. The applicability of the method was tested by analysing three different formulations of IS5MN.     

RF performance of a 418-MHz radio telemeter packaged for humanvaginal placement

The electrical and communication performance of a 0.8-μW UHF temperature telemeter designed for human vaginal placement is discussed; a solenoidal loop antenna was used, occupying a volume of 0.1 cm³ . In situ, measured power absorption was between 19-25 dB, resulting in an effective operating range of 10 m. Capacitive loading lowered the antenna's resonant frequency by 1.4% and there was a significant polarization change in the radiated output     

Differential recruitment of leukocyte populations and alteration of airway hyperreactivity by C-C family chemokines in allergic airway inflammation

Allergic airway inflammation is characterized by peribronchial leukocyte accumulation within the airway. Subsequent tissue damage leading to airway hyperreactivity is a result of activation of multiple leukocyte populations. Using an established model of allergic airway inflammation induced by intratracheal challenge with parasite (Schistosoma mansoni) egg Ag in presensitized mice, we have examined differential leukocyte recruitment. These studies have identified key chemokines involved in the accumulation of specific subsets of cells and the induction of airway hyperreactivity. In this study we have examined three C-C family chemokines, MCP-1, MIP-1alpha, and RANTES, which promote mononuclear cell- and eosinophil-specific recruitment to the airway. The in vivo neutralization of either MIP-1alpha or RANTES, but not MCP-1, significantly reduced the intensity of the eosinophil recruitment to the lung and airway during the allergic airway response by >50 and >60%, respectively. In contrast, neutralization of MCP-1 significantly reduced total leukocyte migration (>50% reduction), whereas neutralization of RANTES and MIP-1alpha had no significant affect on the overall leukocyte migration. Further examination of the effect of MCP-1 depletion indicated that both CD4+ and CD8+ lymphocyte subsets were decreased. Depletion of MCP-1 significantly reduced the airway hyperreactivity to near control levels, whereas depletion of MIP-1alpha or RANTES did not affect the intensity of airway hyperreactivity. These data indicate that multiple C-C chemokines are involved in the recruitment of particular leukocyte populations and that neutralization of MCP-1, but not RANTES or MIP-1alpha, significantly reduced airway hyperreactivity.     

Chimeric bispecific OC/TR monoclonal antibody mediates lysis of tumor cells expressing the folate-binding protein (MOv18) and displays decreased immunogenicity in patients

The current environment in which medicine is taught and practiced requires that medical schools pay increased attention to the faculty member's roles, rewards, career development, and productivity. Medical schools must make strategic decisions about the allocation of resources that can nurture their faculties and support the activities in academic and community settings in which faculty are involved. From 1993 to 1995 Allegheny University of the Health Sciences (formerly Medical College of Pennsylvania and Hahnemann University) designed a comprehensive system for the professional development of faculty. This system is based upon expanded categories of faculty academic activity and scholarship. New programs were implemented to reorient faculty toward conducting and documenting the expanded array of scholarly activities. The main characteristics of the new system are the establishment of formally defined performance expectations, the vertical alignment of the individual faculty member's objectives with the department's mission and the school's mission, and an increasing emphasis upon faculty interdependence, accountability, and use of sound business practices. The authors describe these and other aspects of the design of the new system in detail and report initial results and lessons learned from the system's implementation, evaluation, and dissemination throughout the university. The long-term success of this comprehensive professional development program will be assessed over time by observing how this institution advances its mission in a well-planned and cost-effective manner that retains talented, productive, and professionally fulfilled faculty.     

Intraoperative echocardiography is indicated in high-risk coronary artery bypass grafting

BACKGROUND: Intraoperative echocardiography is a valuable monitoring and diagnostic technology used in cardiac surgery. This reports our clinical study of the usefulness of intraoperative echocardiography to both surgeons and anesthesiologists for high-risk coronary artery bypass grafting. METHODS: From March to November 1995, 82 consecutive high-risk patients undergoing coronary artery bypass grafting were studied in a four-stage protocol to determine the efficacy of intraoperative echocardiography in management planning. Alterations in surgical and anesthetic/hemodynamic management initiated by intraoperative echocardiography findings were documented in addition to perioperative morbidity and mortality. RESULTS: Intraoperative echocardiography initiated at least one major surgical management alteration in 27 patients (33%) and at least one major anesthetic/hemodynamic change in 42 (51%). Mortality and the rate of myocardial infarction in this consecutive high-risk study population using intraoperative echocardiography and in a similar group of patients without the use of intraoperative echocardiography was 1.2% versus 3.8% (not significant) and 1.2% versus 3.5% (not significant), respectively. CONCLUSIONS: We conclude that when all of the isolated diagnostic and monitoring applications of perioperative echocardiography are routinely and systematically performed together, it is a safe and viable tool that significantly affects the decision-making process in the intraoperative care of high-risk patients undergoing primary isolated coronary artery bypass grafting and may contribute to the optimal care of these patients.     

A complication of percutaneous tracheostomy whilst using the Combitube for airway control

A novel bioassay system based on RT-PCR has been established to search for biologically active compounds which can modulate the expression of genes encoding important regulatory proteins. Changes in target mRNA level in the treated cell cultures were quantitatively determined by competitive PCR using internal standard DNA. The compounds discovered using this bioassay will be useful tools to elucidate the mechanisms of cellular signaling guiding the expression of the target genes. As the first application of the new bioassay strategy, the expression of the interleukin-2 gene in Jurkat cells, a human T cell line, was investigated. Screening of several crude drugs used in traditional Chinese medicines demonstrated that the aqueous acetone extract of Coptidis Rhizoma enhanced the expression of the interleukin-2 gene by about 5-fold as compared to the control.