Cocaine cardiotoxicity differs markedly in isolated hearts of two strains of rats exhibiting phenotypic differences in sensitivity to seizures

J. E. Heavner, B. Shi, K. Inners-McBride, G. Asimakis, M. J. Wang, D. C. McIntyre

    Research output: Contribution to journalArticle

    Abstract

    Isolated hearts from two strains of rats bred for sensitivity or resistance to amygdala kindling that also exhibit, in vive differential sensitivity to the cardiotoxicity of cocaine were studied. The goal was to determine if the differential cardiotoxic sensitivity was due, at least in part, to intrinsic strain-dependent differences in the heart. The Langendorff preparation was used (n=8 per strain). Hearts were perfused with increasing concentrations of cocaine (5X10-6, 1X10-5, 5X10-5, 1X10-4, and 5X10- 4 M) for 5 min with a 5 min washout between exposure to successive concentrations. Consistent with in vive observations, hearts from genetically slow amygdala kindling rats (Slow) required lower cocaine doses to develop cardiac arrhythmias and arrest as compared to the hearts from genetically fast amygdala kindling rats (Fast). At 5X10-5M cocaine arrhythmias occurred in 38% (3/8) Slow and 0% Fast hearts. Five of 8 Slow hearts and none of 8 Fast hearts were arrested by 10-4M cocaine: Arrest in Fast hearts occurred only with 5X10-4M cocaine. Cocaine constricted coronary arteries (no significant difference between strains). On the other hand, coronary arteries of Slow but not Fast hearts dilated during cocaine washout after perfusion with all but the highest concentration of cocaine. We conclude that factors intrinsic to the heart and coronary artery influence the sensitivity or response of these structures to cocaine.

    Original languageEnglish (US)
    Pages (from-to)625-633
    Number of pages9
    JournalLife Sciences
    Volume63
    Issue number8
    DOIs
    StatePublished - Jul 17 1998

    Fingerprint

    Cocaine
    Rats
    Seizures
    Amygdala
    Coronary Vessels
    Cardiac Arrhythmias
    Cardiotoxicity
    Intrinsic Factor
    Heart Arrest
    Perfusion

    Keywords

    • Cocaine cardiotoxicology
    • Coronary artery
    • Differential sensitivity
    • Kindling
    • Langendorff preparation
    • Rats

    ASJC Scopus subject areas

    • Pharmacology

    Cite this

    Cocaine cardiotoxicity differs markedly in isolated hearts of two strains of rats exhibiting phenotypic differences in sensitivity to seizures. / Heavner, J. E.; Shi, B.; Inners-McBride, K.; Asimakis, G.; Wang, M. J.; McIntyre, D. C.

    In: Life Sciences, Vol. 63, No. 8, 17.07.1998, p. 625-633.

    Research output: Contribution to journalArticle

    Heavner, J. E. ; Shi, B. ; Inners-McBride, K. ; Asimakis, G. ; Wang, M. J. ; McIntyre, D. C. / Cocaine cardiotoxicity differs markedly in isolated hearts of two strains of rats exhibiting phenotypic differences in sensitivity to seizures. In: Life Sciences. 1998 ; Vol. 63, No. 8. pp. 625-633.
    @article{4e7bd52d3dcd49dab6bddc843669a18e,
    title = "Cocaine cardiotoxicity differs markedly in isolated hearts of two strains of rats exhibiting phenotypic differences in sensitivity to seizures",
    abstract = "Isolated hearts from two strains of rats bred for sensitivity or resistance to amygdala kindling that also exhibit, in vive differential sensitivity to the cardiotoxicity of cocaine were studied. The goal was to determine if the differential cardiotoxic sensitivity was due, at least in part, to intrinsic strain-dependent differences in the heart. The Langendorff preparation was used (n=8 per strain). Hearts were perfused with increasing concentrations of cocaine (5X10-6, 1X10-5, 5X10-5, 1X10-4, and 5X10- 4 M) for 5 min with a 5 min washout between exposure to successive concentrations. Consistent with in vive observations, hearts from genetically slow amygdala kindling rats (Slow) required lower cocaine doses to develop cardiac arrhythmias and arrest as compared to the hearts from genetically fast amygdala kindling rats (Fast). At 5X10-5M cocaine arrhythmias occurred in 38{\%} (3/8) Slow and 0{\%} Fast hearts. Five of 8 Slow hearts and none of 8 Fast hearts were arrested by 10-4M cocaine: Arrest in Fast hearts occurred only with 5X10-4M cocaine. Cocaine constricted coronary arteries (no significant difference between strains). On the other hand, coronary arteries of Slow but not Fast hearts dilated during cocaine washout after perfusion with all but the highest concentration of cocaine. We conclude that factors intrinsic to the heart and coronary artery influence the sensitivity or response of these structures to cocaine.",
    keywords = "Cocaine cardiotoxicology, Coronary artery, Differential sensitivity, Kindling, Langendorff preparation, Rats",
    author = "Heavner, {J. E.} and B. Shi and K. Inners-McBride and G. Asimakis and Wang, {M. J.} and McIntyre, {D. C.}",
    year = "1998",
    month = "7",
    day = "17",
    doi = "10.1016/S0024-3205(98)00314-2",
    language = "English (US)",
    volume = "63",
    pages = "625--633",
    journal = "Life Sciences",
    issn = "0024-3205",
    publisher = "Elsevier Inc.",
    number = "8",

    }

    TY - JOUR

    T1 - Cocaine cardiotoxicity differs markedly in isolated hearts of two strains of rats exhibiting phenotypic differences in sensitivity to seizures

    AU - Heavner, J. E.

    AU - Shi, B.

    AU - Inners-McBride, K.

    AU - Asimakis, G.

    AU - Wang, M. J.

    AU - McIntyre, D. C.

    PY - 1998/7/17

    Y1 - 1998/7/17

    N2 - Isolated hearts from two strains of rats bred for sensitivity or resistance to amygdala kindling that also exhibit, in vive differential sensitivity to the cardiotoxicity of cocaine were studied. The goal was to determine if the differential cardiotoxic sensitivity was due, at least in part, to intrinsic strain-dependent differences in the heart. The Langendorff preparation was used (n=8 per strain). Hearts were perfused with increasing concentrations of cocaine (5X10-6, 1X10-5, 5X10-5, 1X10-4, and 5X10- 4 M) for 5 min with a 5 min washout between exposure to successive concentrations. Consistent with in vive observations, hearts from genetically slow amygdala kindling rats (Slow) required lower cocaine doses to develop cardiac arrhythmias and arrest as compared to the hearts from genetically fast amygdala kindling rats (Fast). At 5X10-5M cocaine arrhythmias occurred in 38% (3/8) Slow and 0% Fast hearts. Five of 8 Slow hearts and none of 8 Fast hearts were arrested by 10-4M cocaine: Arrest in Fast hearts occurred only with 5X10-4M cocaine. Cocaine constricted coronary arteries (no significant difference between strains). On the other hand, coronary arteries of Slow but not Fast hearts dilated during cocaine washout after perfusion with all but the highest concentration of cocaine. We conclude that factors intrinsic to the heart and coronary artery influence the sensitivity or response of these structures to cocaine.

    AB - Isolated hearts from two strains of rats bred for sensitivity or resistance to amygdala kindling that also exhibit, in vive differential sensitivity to the cardiotoxicity of cocaine were studied. The goal was to determine if the differential cardiotoxic sensitivity was due, at least in part, to intrinsic strain-dependent differences in the heart. The Langendorff preparation was used (n=8 per strain). Hearts were perfused with increasing concentrations of cocaine (5X10-6, 1X10-5, 5X10-5, 1X10-4, and 5X10- 4 M) for 5 min with a 5 min washout between exposure to successive concentrations. Consistent with in vive observations, hearts from genetically slow amygdala kindling rats (Slow) required lower cocaine doses to develop cardiac arrhythmias and arrest as compared to the hearts from genetically fast amygdala kindling rats (Fast). At 5X10-5M cocaine arrhythmias occurred in 38% (3/8) Slow and 0% Fast hearts. Five of 8 Slow hearts and none of 8 Fast hearts were arrested by 10-4M cocaine: Arrest in Fast hearts occurred only with 5X10-4M cocaine. Cocaine constricted coronary arteries (no significant difference between strains). On the other hand, coronary arteries of Slow but not Fast hearts dilated during cocaine washout after perfusion with all but the highest concentration of cocaine. We conclude that factors intrinsic to the heart and coronary artery influence the sensitivity or response of these structures to cocaine.

    KW - Cocaine cardiotoxicology

    KW - Coronary artery

    KW - Differential sensitivity

    KW - Kindling

    KW - Langendorff preparation

    KW - Rats

    UR - http://www.scopus.com/inward/record.url?scp=0032541110&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0032541110&partnerID=8YFLogxK

    U2 - 10.1016/S0024-3205(98)00314-2

    DO - 10.1016/S0024-3205(98)00314-2

    M3 - Article

    VL - 63

    SP - 625

    EP - 633

    JO - Life Sciences

    JF - Life Sciences

    SN - 0024-3205

    IS - 8

    ER -