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Comparative myocardial toxicity of two halogenated solvents
161 dOdPARATIVE MYOCARDIAL TOXICITY OF TWO RALCGENATED SOLVENTS
ZAKRARI, S. CORPORATION 11140 ROCKVILLE PIKE ROCKVILLE, MARYLAND 20852 DYNAMAC
U.S.A.
The cardiovascular toxicity of 1,1,2-trichloro-1,2,2_trifluoroethane (Freon 113) and 1,2-dichloro-2,2-difluoroethane (Freon 132b) was studied in anesthetized open-chest dogs. The freons mixed with air were administered by inhalation for 5 minutes at concentrations of 1.0, 2.5, 5.0 or 10.0% v/v. The following parametersweremeasured: arterial pressure (API, left ventricular pressure(LVP), left ventricular derivative (dP/dt)max, myocardial contractile force (MCF), cardiac output (COP), coronary blood flow (CBF), and heart rate. Roth solvents induced a decrease in all measured parameters (see table below). However, Freon 113 was more cardiotoxic than Freon 132b at low concentrations (1%). At higher concentrations (5% and lo%), both solvents exhibited similar magnitude of myocardial depression. Furthermore, Freon 113 sensitized the heart to epinephrine challenge, whereas Freon 13Zb did not. Average Decrease in Measured Parameters Concentration Freon
1%
(v/v)
AP (mean) LVP (dp/dtlmax MCF COP CBF
(% of Control)
5%
10%
113
132b
113
132b
113
132b-
15.4* 16.4. 21.9* 8.7*
1.9 2.9* 4.a* 5.6"
37.2* 35.6* 42.3* 26.5,
26.5" 30.2* 43.5* 26.7'
56.4* 56.3' 65.5. 38.7'
54.2. 57.1' 67.5* 58.8*
13.5*
5.0
30.5’
24.2’
39.2.
57.1*
10.9*
5.2
27.6*
17.2*
49.7'
57.7*
*Statistically significant change.
DITHIOL METAL BINDING AGENTS - EFFICACIES AND PROPERTIES IN VIVO AND IN VITRO. MAIORINO, R., HSU, C.A., STINE, E.R., HOOVER, T.D., APCSHIAN, H-V. UNIVERSITY OF ARIZONA, TUCSON, ARIZONA 85721 tJSA
UNIVERSITY OF ARIZONA CELLULAR'AND DEVELOPMENTAL BIOLOGY BIOSCIENCES WEST, RM. 262 TUCSON, ARIZONA 85721 USA Dimercaptopropanesulfonate (DMPS), meso-dimercaptosuccinic acid (DMSA) and N-(2,3-dimercaptopropyl)-phthalamidicacid (DMPA) are water soluble metal binding agents that have advantages when comoared to their analog BAL. Recent experiments in this. laboratory have compared these agents with lipid soluble BAL in mice and can be summarized as follows:
LD50 (mmols/kg) ip ED50 (mmols/kgl ip Median Therapeutic Index
BAL 1.53 0.182 8.40
DMSA 13.73 0.037 369.
DMPS 6.53 0.055 119.
DMPA -0.83 0.025 33.2
The ED58 value applies to male mice given 0.15 mm01 NaAs02/kg, scI ten The activity of any one of these minutes before the dithiol camp As in rabbits is greater than that of compounds in mobilizing tissue 3Yd' BAL and the latter increases brain levels of 74As. DMPS is more potent the inhib' ion by sodium arsenite of than DMSA in reversing, in vivo, When IfC-DMPS is qiven to rabbits, the pyruvate dehydrogenase complex. DMPS, as.such, cannot be detected in the urine as shown by TLC and spectrophotometric
assays.
ZAKRARI, S. CORPORATION 11140 ROCKVILLE PIKE ROCKVILLE, MARYLAND 20852 DYNAMAC
U.S.A.
The cardiovascular toxicity of 1,1,2-trichloro-1,2,2_trifluoroethane (Freon 113) and 1,2-dichloro-2,2-difluoroethane (Freon 132b) was studied in anesthetized open-chest dogs. The freons mixed with air were administered by inhalation for 5 minutes at concentrations of 1.0, 2.5, 5.0 or 10.0% v/v. The following parametersweremeasured: arterial pressure (API, left ventricular pressure(LVP), left ventricular derivative (dP/dt)max, myocardial contractile force (MCF), cardiac output (COP), coronary blood flow (CBF), and heart rate. Roth solvents induced a decrease in all measured parameters (see table below). However, Freon 113 was more cardiotoxic than Freon 132b at low concentrations (1%). At higher concentrations (5% and lo%), both solvents exhibited similar magnitude of myocardial depression. Furthermore, Freon 113 sensitized the heart to epinephrine challenge, whereas Freon 13Zb did not. Average Decrease in Measured Parameters Concentration Freon
1%
(v/v)
AP (mean) LVP (dp/dtlmax MCF COP CBF
(% of Control)
5%
10%
113
132b
113
132b
113
132b-
15.4* 16.4. 21.9* 8.7*
1.9 2.9* 4.a* 5.6"
37.2* 35.6* 42.3* 26.5,
26.5" 30.2* 43.5* 26.7'
56.4* 56.3' 65.5. 38.7'
54.2. 57.1' 67.5* 58.8*
13.5*
5.0
30.5’
24.2’
39.2.
57.1*
10.9*
5.2
27.6*
17.2*
49.7'
57.7*
*Statistically significant change.
DITHIOL METAL BINDING AGENTS - EFFICACIES AND PROPERTIES IN VIVO AND IN VITRO. MAIORINO, R., HSU, C.A., STINE, E.R., HOOVER, T.D., APCSHIAN, H-V. UNIVERSITY OF ARIZONA, TUCSON, ARIZONA 85721 tJSA
UNIVERSITY OF ARIZONA CELLULAR'AND DEVELOPMENTAL BIOLOGY BIOSCIENCES WEST, RM. 262 TUCSON, ARIZONA 85721 USA Dimercaptopropanesulfonate (DMPS), meso-dimercaptosuccinic acid (DMSA) and N-(2,3-dimercaptopropyl)-phthalamidicacid (DMPA) are water soluble metal binding agents that have advantages when comoared to their analog BAL. Recent experiments in this. laboratory have compared these agents with lipid soluble BAL in mice and can be summarized as follows:
LD50 (mmols/kg) ip ED50 (mmols/kgl ip Median Therapeutic Index
BAL 1.53 0.182 8.40
DMSA 13.73 0.037 369.
DMPS 6.53 0.055 119.
DMPA -0.83 0.025 33.2
The ED58 value applies to male mice given 0.15 mm01 NaAs02/kg, scI ten The activity of any one of these minutes before the dithiol camp As in rabbits is greater than that of compounds in mobilizing tissue 3Yd' BAL and the latter increases brain levels of 74As. DMPS is more potent the inhib' ion by sodium arsenite of than DMSA in reversing, in vivo, When IfC-DMPS is qiven to rabbits, the pyruvate dehydrogenase complex. DMPS, as.such, cannot be detected in the urine as shown by TLC and spectrophotometric
assays.