Hypotension and cardiac arrest have been observed in patients anesthetized with the anesthetics, halothane, enflurane, and thiopental. These anesthetics are in wide clinical use today. Preliminary evidence suggests that these anesthetics might decrease the availability of Ca++ required for cardiac contraction. This project is designed to study the effect of the above mentioned anesthetics on structures in the myocardial cell that regulate Ca++ flux and control the intensity of contraction. The elements that will be studies are: the sarcolemma (SL), the outer membrane of the muscle cell; the sarcoplasmic reticulum (SR), a membranous network that controls the amount of mypolasmic Ca++; and troponin (Tn), a protein that responds to Ca++ binding by changing its shape and initiating the contractile process. Present evidence suggests that the SR is affected by anesthetics but may not be the major site of alteration of contractility. The studies outlined will examine the interaction of halothane, enflurane, and thiopental with the subcellular structures to observe alterations in Ca++ response. The results wll quantify the relative effect of each anesthetic on each structure and a possible mechanism of action will be postulated. The data obtained will help in formulating pharmacologic interventions to prevent anesthetic-induced cardiac depression in the operating room.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030799-05
Application #
3278682
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1981-11-01
Project End
1986-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Sarti, P; Silver, R B; Paroli, L et al. (1999) Permeability of rat heart myocytes to cytochrome c. Cell Mol Life Sci 56:1061-9
Andoh, T; Blanck, T J; Nikonorov, I et al. (1997) Volatile anaesthetic effects on calcium conductance of planar lipid bilayers formed with synthetic lipids or extracted lipids from sarcoplasmic reticulum. Br J Anaesth 78:66-74
Blanck, T J; Yasukochi, S; Quigg, M et al. (1997) Global ischemia increases the density of voltage-dependent calcium channels in porcine cardiac sarcolemma. Anesth Analg 84:972-5
Meyers, M B; Zamparelli, C; Verzili, D et al. (1995) Calcium-dependent translocation of sorcin to membranes: functional relevance in contractile tissue. FEBS Lett 357:230-4
Blanck, T J; Lee, D L; Yasukochi, S et al. (1994) The role of L-type voltage-dependent calcium channels in anesthetic depression of contractility. Adv Pharmacol 31:207-14
Sarti, P; Antonini, G; Arancia, G et al. (1994) Lonidamine-mediated respiratory changes in rat heart myocytes: a re-examination of the functional response of mitochondrial cytochrome c oxidase. Biochem Pharmacol 47:2221-5
Lee, D L; Zhang, J; Blanck, T J (1994) The effects of halothane on voltage-dependent calcium channels in isolated Langendorff-perfused rat heart. Anesthesiology 81:1212-9
Antonini, G; Malatesta, F; Sarti, P et al. (1993) Time-resolved optical spectroscopy on intact myocytes. Cardioscience 4:41-6
Sarti, P; Antonini, G; Malatesta, F et al. (1992) Spectral analysis of cytochromes in rat heart myocytes: transient and steady-state photodiode array spectrophotometry measurements. Arch Biochem Biophys 299:8-14
Blanck, T J; Peterson, C V; Baroody, B et al. (1992) Halothane, enflurane, and isoflurane stimulate calcium leakage from rabbit sarcoplasmic reticulum. Anesthesiology 76:813-21

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