The objective of the proposed research is to study the mechanisms of action of anesthetics on the depression of myocardial contractility in diseased cardiac muscle isolated from rabbits or biopsied from humans. It is hypothesized that the sarcoplasmic reticulum (SR) in diseased as well as normal cardiac muscle is the major site of action of anesthetics. To test the hypothesis, we will study the mechanisms of anesthetic action on diseased cardiac muscle, as follows: (1) the effects of the drugs on intracellular sites of muscle contraction, that is, activation of contractile proteins by calcium and calcium uptake, and by release from the SR in skinned muscle fibers, (2) the effects of the drugs on calcium binding to isolated troponin C, (3) the effects of the drugs on calcium uptake, calcium release, and SR-ATPase activity of the SR in isolated SR, and (4) the effects of the drugs on calcium content in the SR of skinned fibers using electron probe microanalysis. The above effects of the anesthetics on the intracellular sites of muscle contraction will be correlated with those on isometric twitch tension of isolated intact papillary muscle preparations. Our long-term goal is to study the mechanisms of action of anesthetics and anesthesia-related drugs on cardiac muscle from other diseased states, such as hypertension, hyperthyroidism, diabetes, malnutrition, and skeletal muscle myopathies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL020754-12
Application #
3336252
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1977-04-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
12
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Sivarajan, M; Su, J Y; Hofer, B O (1995) Effects of halothane on calcium(2+)-activated tension of the contractile proteins and calcium(2+) uptake and release by the sarcoplasmic reticulum in skinned human myocardial fibers. Anesth Analg 81:52-6
Su, J Y; Chang, Y I (1993) Modulation of sarcoplasmic reticulum Ca(2+)-release channels by caffeine, Ca2+, and Mg2+ in skinned myocardial fibers of fetal and adult rats. Pflugers Arch 423:300-6
Rooke, G A; Su, J Y (1993) The effect of halothane on the sarcoplasmic reticulum in normal and right ventricular hypertrophy in rabbits. Anesth Analg 77:1091-7
Rooke, G A; Su, J Y (1992) Left ventricular hypertrophy in rabbits does not exaggerate the effects of halothane on the intracellular components of cardiac contraction. Anesthesiology 77:513-21
Su, J Y (1992) Influence of caffeine, Ca2+, and Mg2+ on ryanodine depression of the tension transient in skinned myocardial fibers of the rabbit. Pflugers Arch 421:1-6
Su, J Y (1992) Effects of ryanodine on SR Ca2+ release channels demonstrated with caffeine-induced tension transients in skinned striated and vascular smooth muscle. Adv Exp Med Biol 311:439-43
Zhang, C C; Su, J Y; Calkins, D (1990) Effects of alfentanil on isolated cardiac tissues of the rabbit. Anesth Analg 71:268-74
Krane, E J; Su, J Y (1989) Comparison of the effects of halothane on skinned myocardial fibers from newborn and adult rabbit. I. Effects on contractile proteins. Anesthesiology 70:76-81
Krane, E J; Su, J Y (1989) Comparison of the effects of halothane on skinned myocardial fibers from newborn and adult rabbit: II. Effects on sarcoplasmic reticulum. Anesthesiology 71:103-9
Su, J Y; Zhang, C C (1989) Intracellular mechanisms of halothane's effect on isolated aortic strips of the rabbit. Anesthesiology 71:409-17

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