Abstract
Abnormal myocardial composition in diabetes mellitus has been described, but the effects on ventricular vulnerability have not been defined. We have assessed the susceptibility to arrhythmias in a canine model after 1 yr of mild diabetes induced by alloxan. Since physical conditioning can affect metabolic abnormalities in diabetes, this intervention has also been evaluated. Group 1 served as controls and groups 3 and 4 were diabetic. Animals in the latter group as well as nondiabetic controls of group 2 were exercised on a treadmill for the last 8 mo of the experiment. After 1 yr, anesthesia was induced with chloralose for vulnerability studies. The ventricular fibrillation threshold of 24.4 +/- 1.9 mA in group 3 was significantly less than in normals (45.1 +/- 2.2). Spontaneous arrhythmias were also more prevalent in diabetics during acute ischemia (group 3-A). Increased ventricular vulnerability after epinephrine infusion was present in the sedentary diabetes despite normal ventricular function responsiveness. In a superfused preparation of myocardium, resting membrane potential and action potential amplitude were normal in diabetics, and beta-adrenergic stimulation shortened repolarization more than in controls. Myocardial collagen concentrations, which included an interfibrillar distribution on morphologic examination, were increased in group 3. In the trained diabetics of group 4 the basal vulnerability thresholds and responses to epinephrine were normal. While myocardial collagen levels were normal, cholesterol and triglyceride increments persisted. Thus, in mild experimental diabetes, enhanced susceptibility to arrhythmias exists; this susceptibility may be based on a combination of nonhomogenous collagen accumulation affecting local conduction and increased electrophysiologic sensitivity to catecholamines.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
- Baandrup U., Olsen E. G. Critical analysis of endomyocardial biopsies from patients suspected of having cardiomyopathy. I: Morphological and morphometric aspects. Br Heart J. 1981 May;45(5):475–486. doi: 10.1136/hrt.45.5.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Billman G. E., Schwartz P. J., Stone H. L. The effects of daily exercise on susceptibility to sudden cardiac death. Circulation. 1984 Jun;69(6):1182–1189. doi: 10.1161/01.cir.69.6.1182. [DOI] [PubMed] [Google Scholar]
- Brooks W. W., Verrier R. L., Lown B. Influence of vagal tone on stellectomy-induced changes in ventricular electrical stability. Am J Physiol. 1978 May;234(5):H503–H507. doi: 10.1152/ajpheart.1978.234.5.H503. [DOI] [PubMed] [Google Scholar]
- Caspari P. G., Newcomb M., Gibson K., Harris P. Collagen in the normal and hypertrophied human ventricle. Cardiovasc Res. 1977 Nov;11(6):554–558. doi: 10.1093/cvr/11.6.554. [DOI] [PubMed] [Google Scholar]
- Coker S. J., Parratt J. R. Nifedipine reduces arrhythmias but does not alter prostanoid release during coronary artery occlusion and reperfusion in anaesthetised greyhounds. J Cardiovasc Pharmacol. 1983 May-Jun;5(3):406–417. doi: 10.1097/00005344-198305000-00010. [DOI] [PubMed] [Google Scholar]
- Conlee R. K., Tipton C. M. Cardiac glycogen repletion after exercise: influence of synthase and glucose 6-phosphate. J Appl Physiol Respir Environ Exerc Physiol. 1977 Feb;42(2):240–244. doi: 10.1152/jappl.1977.42.2.240. [DOI] [PubMed] [Google Scholar]
- Cryer P. E. Isotope-derivative measurements of plasma norepinephrine and epinephrine in man. Diabetes. 1976 Nov;25(11):1071–1082. doi: 10.2337/diab.25.11.1071. [DOI] [PubMed] [Google Scholar]
- Ettinger P. O., Khan M. I., Regan T. J. A catheter electrode technique for study of left ventricular conduction. J Appl Physiol. 1970 Apr;28(4):519–523. doi: 10.1152/jappl.1970.28.4.519. [DOI] [PubMed] [Google Scholar]
- Ettinger P. O., Lyons M., Oldewurtel H. A., Regan T. J. Cardiac conduction abnormalities produced by chronic alcoholism. Am Heart J. 1976 Jan;91(1):66–78. doi: 10.1016/s0002-8703(76)80436-x. [DOI] [PubMed] [Google Scholar]
- Euler D. E., Moore E. N. Continuous fractionated electrical activity after stimulation of the ventricles during the vulnerable period: evidence for local reentry. Am J Cardiol. 1980 Nov;46(5):783–791. doi: 10.1016/0002-9149(80)90429-4. [DOI] [PubMed] [Google Scholar]
- Euler D. E. Norepinephrine release by ventricular stimulation: effect on fibrillation thresholds. Am J Physiol. 1980 Mar;238(3):H406–H413. doi: 10.1152/ajpheart.1980.238.3.H406. [DOI] [PubMed] [Google Scholar]
- Fein F. S., Aronson R. S., Nordin C., Miller-Green B., Sonnenblick E. H. Altered myocardial response to ouabain in diabetic rats: mechanics and electrophysiology. J Mol Cell Cardiol. 1983 Nov;15(11):769–784. doi: 10.1016/0022-2828(83)90336-x. [DOI] [PubMed] [Google Scholar]
- Friedman P. L., Stewart J. R., Fenoglio J. J., Jr, Wit A. L. Survival of subendocardial Purkinje fibers after extensive myocardial infarction in dogs. Circ Res. 1973 Nov;33(5):597–611. doi: 10.1161/01.res.33.5.597. [DOI] [PubMed] [Google Scholar]
- Giacomelli F., Wiener J. Primary myocardial disease in the diabetic mouse. An ultrastructural study. Lab Invest. 1979 Apr;40(4):460–473. [PubMed] [Google Scholar]
- HILL J. B., KESSLER G. An automated determination of glucose utilizing a glucose oxidase-peroxidase system. J Lab Clin Med. 1961 Jun;57:970–980. [PubMed] [Google Scholar]
- Haider B., Ahmed S. S., Moschos C. B., Oldewurtel H. A., Regan T. J. Myocardial function and coronary blood flow response to acute ischemia in chronic canine diabetes. Circ Res. 1977 Jun;40(6):577–583. doi: 10.1161/01.res.40.6.577. [DOI] [PubMed] [Google Scholar]
- Haider B., Khan M. I., Burke W. M., Regan T. J. Ischemic heart failure: sustained inotropic response to small doses of I-epinephrine without toxicity. Am J Cardiol. 1975 Apr;35(4):504–513. doi: 10.1016/0002-9149(75)90833-4. [DOI] [PubMed] [Google Scholar]
- Haider B., Yeh C. K., Thomas G., Oldewurtel H. A., Lyons M. M., Regan T. J. Influence of diabetes on the myocardium and coronary arteries of rhesus monkey fed an atherogenic diet. Circ Res. 1981 Dec;49(6):1278–1288. doi: 10.1161/01.res.49.6.1278. [DOI] [PubMed] [Google Scholar]
- Hoyt R. H., Ericksen E., Collins S. M., Skorton D. J. Computer-assisted quantitation of myocardial fibrosis in histologic sections. Arch Pathol Lab Med. 1984 Apr;108(4):280–283. [PubMed] [Google Scholar]
- Issekutz B., Jr, Shaw W. A. Glucose turnover in the exercising dog with chemically induced diabetes and the effect of methylprednisolone. Diabetes. 1975 Oct;24(10):915–921. doi: 10.2337/diab.24.10.915. [DOI] [PubMed] [Google Scholar]
- Jaillon P., Schnittger I., Griffin J. C., Winkle R. A. The relationship between the repetitive extrasystole threshold and the ventricular fibrillation threshold in the dog. Non-parallel changes following pharmacological intervention. Circ Res. 1980 May;46(5):599–605. doi: 10.1161/01.res.46.5.599. [DOI] [PubMed] [Google Scholar]
- Jarrett R. J., McCartney P., Keen H. The Bedford survey: ten year mortality rates in newly diagnosed diabetics, borderline diabetics and normoglycaemic controls and risk indices for coronary heart disease in borderline diabetics. Diabetologia. 1982 Feb;22(2):79–84. doi: 10.1007/BF00254833. [DOI] [PubMed] [Google Scholar]
- KELLEY T. F. IMPROVED METHOD FOR MICROTITRATION OF FATTY ACIDS. Anal Chem. 1965 Jul;37:1078–1079. doi: 10.1021/ac60227a044. [DOI] [PubMed] [Google Scholar]
- Kaplinsky E., Ogawa S., Balke C. W., Dreifus L. S. Two periods of early ventricular arrhythmia in the canine acute myocardial infarction model. Circulation. 1979 Aug;60(2):397–403. doi: 10.1161/01.cir.60.2.397. [DOI] [PubMed] [Google Scholar]
- Kent K. M., Smith E. R., Redwood D. R., Epstein S. E. Electrical stability of acutely ischemic myocardium. Influences of heart rate and vagal stimulation. Circulation. 1973 Feb;47(2):291–298. doi: 10.1161/01.cir.47.2.291. [DOI] [PubMed] [Google Scholar]
- Klenk D. C., Hermanson G. T., Krohn R. I., Fujimoto E. K., Mallia A. K., Smith P. K., England J. D., Wiedmeyer H. M., Little R. R., Goldstein D. E. Determination of glycosylated hemoglobin by affinity chromatography: comparison with colorimetric and ion-exchange methods, and effects of common interferences. Clin Chem. 1982 Oct;28(10):2088–2094. [PubMed] [Google Scholar]
- Kowey P. R., Verrier R. L., Lown B. Decreased vulnerability to ventricular fibrillation by vasodilator-induced baroreceptor sensitisation. Cardiovasc Res. 1983 Feb;17(2):106–112. doi: 10.1093/cvr/17.2.106. [DOI] [PubMed] [Google Scholar]
- LEVINE H. J., BRITMAN N. A. FORCE-VELOCITY RELATIONS IN THE INTACT DOG HEART. J Clin Invest. 1964 Jul;43:1383–1396. doi: 10.1172/JCI105014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEVINE J. B., ZAK B. AUTOMATED DETERMINATION OF SERUM TOTAL CHOLESTEROL. Clin Chim Acta. 1964 Oct;10:381–384. doi: 10.1016/0009-8981(64)90073-7. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., PASSONNEAU J. V., HASSELBERGER F. X., SCHULZ D. W. EFFECT OF ISCHEMIA ON KNOWN SUBSTRATES AND COFACTORS OF THE GLYCOLYTIC PATHWAY IN BRAIN. J Biol Chem. 1964 Jan;239:18–30. [PubMed] [Google Scholar]
- Liang B., Verrier R. L., Melman J., Lown B. Correlation between circulating catecholamine levels and ventricular vulnerability during psychological stress in conscious dogs. Proc Soc Exp Biol Med. 1979 Jul;161(3):266–269. doi: 10.3181/00379727-161-40533. [DOI] [PubMed] [Google Scholar]
- Matta R. J., Verrier R. L., Lown B. Repetitive extrasystole as an index of vulnerability to ventricular fibrillation. Am J Physiol. 1976 Jun;230(6):1469–1473. doi: 10.1152/ajplegacy.1976.230.6.1469. [DOI] [PubMed] [Google Scholar]
- Merx W., Yoon M. S., Han J. The role of local disparity in conduction and recovery time on ventricular vulnerability to fibrillation. Am Heart J. 1977 Nov;94(5):603–610. doi: 10.1016/s0002-8703(77)80130-0. [DOI] [PubMed] [Google Scholar]
- Modrak J. Collagen metabolism in the myocardium from streptozotocin-diabetic rats. Diabetes. 1980 Jul;29(7):547–550. doi: 10.2337/diab.29.7.547. [DOI] [PubMed] [Google Scholar]
- Munakata K., Dominic J. A., Surawicz B. Variable effects of isoproterenol on action potential duration in guinea-pig papillary muscle: differences between nonsteady and steady state; role of extracellular calcium concentration. J Pharmacol Exp Ther. 1982 Jun;221(3):806–814. [PubMed] [Google Scholar]
- Nattel S., Pedersen D. H., Zipes D. P. Alterations in regional myocardial distribution and arrhythmogenic effects of aprindine produced by coronary artery occlusion in the dog. Cardiovasc Res. 1981 Feb;15(2):80–85. doi: 10.1093/cvr/15.2.80. [DOI] [PubMed] [Google Scholar]
- Niehues B., Schwanitz V., Hagemann K., Manoli S., Oswald S., Arnold G., Lochner W. Die Bedeutung von dp-dtmax für die Beurteilung der Kontraktilität rechten Ventrikels. Z Kardiol. 1973 Nov;62(11):1029–1040. [PubMed] [Google Scholar]
- Nivatpumin T., Katz S., Scheuer J. Peak left ventricular systolic pressure/end-systolic volume ratio: a sensitive detector of left ventricular disease. Am J Cardiol. 1979 May;43(5):969–974. doi: 10.1016/0002-9149(79)90361-8. [DOI] [PubMed] [Google Scholar]
- Noakes T. D., Higginson L., Opie L. H. Physical training increases ventricular fibrillation thresholds of isolated rat hearts during normoxia, hypoxia and regional ischemia. Circulation. 1983 Jan;67(1):24–30. doi: 10.1161/01.cir.67.1.24. [DOI] [PubMed] [Google Scholar]
- Nordin C., Gilat E., Aronson R. S. Delayed afterdepolarizations and triggered activity in ventricular muscle from rats with streptozotocin-induced diabetes. Circ Res. 1985 Jul;57(1):28–34. doi: 10.1161/01.res.57.1.28. [DOI] [PubMed] [Google Scholar]
- Obeid A. I., Verrier R. L., Lown B. Influence of glucose, insulin, and potassium on vulnerability to ventricular fibrillation in the canine heart. Circ Res. 1978 Oct;43(4):601–608. doi: 10.1161/01.res.43.4.601. [DOI] [PubMed] [Google Scholar]
- PROCKOP D. J., UDENFRIEND S. A specific method for the analysis of hydroxyproline in tissues and urine. Anal Biochem. 1960 Nov;1:228–239. doi: 10.1016/0003-2697(60)90050-6. [DOI] [PubMed] [Google Scholar]
- Pain V. M., Garlick P. J. Effect of streptozotocin diabetes and insulin treatment on the rate of protein synthesis in tissues of the rat in vivo. J Biol Chem. 1974 Jul 25;249(14):4510–4514. [PubMed] [Google Scholar]
- Penpargkul S., Schaible T., Yipintsoi T., Scheuer J. The effect of diabetes on performance and metabolism of rat hearts. Circ Res. 1980 Dec;47(6):911–921. doi: 10.1161/01.res.47.6.911. [DOI] [PubMed] [Google Scholar]
- Pierce G. N., Kutryk M. J., Dhalla N. S. Alterations in Ca2+ binding by and composition of the cardiac sarcolemmal membrane in chronic diabetes. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5412–5416. doi: 10.1073/pnas.80.17.5412. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Regan T. J., Lyons M. M., Ahmed S. S., Levinson G. E., Oldewurtel H. A., Ahmad M. R., Haider B. Evidence for cardiomyopathy in familial diabetes mellitus. J Clin Invest. 1977 Oct;60(4):884–899. doi: 10.1172/JCI108843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Regan T. J., Wu C. F., Yeh C. K., Oldewurtel H. A., Haider B. Myocardial composition and function in diabetes. The effects of chronic insulin use. Circ Res. 1981 Dec;49(6):1268–1277. doi: 10.1161/01.res.49.6.1268. [DOI] [PubMed] [Google Scholar]
- Roe J. H., Dailey R. E. Determination of glycogen with the anthrone reagent. Anal Biochem. 1966 May;15(2):245–250. doi: 10.1016/0003-2697(66)90028-5. [DOI] [PubMed] [Google Scholar]
- Rosen K. M., Rahimtoola S. H., Sinno M. Z., Gunnar R. M. Bundle branch and ventricular activation in man: a study using catheter recordings of left and right bundle branch potentials. Circulation. 1971 Feb;43(2):193–203. doi: 10.1161/01.cir.43.2.193. [DOI] [PubMed] [Google Scholar]
- Scheuer J., Penpargkul S., Bhan A. K. Experimental observations on the effects of physical training upon intrinsic cardiac physiology and biochemistry. Am J Cardiol. 1974 May 20;33(6):744–751. doi: 10.1016/0002-9149(74)90215-x. [DOI] [PubMed] [Google Scholar]
- Sethi V., Haider B., Ahmed S. S., Oldewurtel H. A., Regan T. J. Influence of beta blockade and chemical sympathectomy on myocardial function and arrhythmias in acute ischaemia. Cardiovasc Res. 1973 Nov;7(6):740–747. doi: 10.1093/cvr/7.6.740. [DOI] [PubMed] [Google Scholar]
- Spach M. S., Miller W. T., 3rd, Geselowitz D. B., Barr R. C., Kootsey J. M., Johnson E. A. The discontinuous nature of propagation in normal canine cardiac muscle. Evidence for recurrent discontinuities of intracellular resistance that affect the membrane currents. Circ Res. 1981 Jan;48(1):39–54. doi: 10.1161/01.res.48.1.39. [DOI] [PubMed] [Google Scholar]
- Stuesse S. L., Wallick D. W., Mace S. Vagal control of heart period in alloxan diabetic rats. Life Sci. 1982 Jul 26;31(4):393–398. doi: 10.1016/0024-3205(82)90420-9. [DOI] [PubMed] [Google Scholar]
- Vadlamudi R. V., McNeill J. H. Effect of experimental diabetes on rat cardiac cAMP, phosphorylase, and inotropy. Am J Physiol. 1983 Jun;244(6):H844–H851. doi: 10.1152/ajpheart.1983.244.6.H844. [DOI] [PubMed] [Google Scholar]
- Wyatt H. L., Mitchell J. H. Influences of physical training on the heart of dogs. Circ Res. 1974 Dec;35(6):883–889. doi: 10.1161/01.res.35.6.883. [DOI] [PubMed] [Google Scholar]