Temporal Characteristics of Phenotypic Alteration and its Functional Correlate in the STZ-induced Diabetic Rat Heart: Preliminary Observations

University College Dublin (2009) Proc Physiol Soc 15, PC104

Poster Communications: Temporal Characteristics of Phenotypic Alteration and its Functional Correlate in the STZ-induced Diabetic Rat Heart: Preliminary Observations

A. D'Souza1, N. M. Woods1, J. Singh1

1. School of Forensic and Investigative Science, University of Central Lancashire, Preston, Lancashire, United Kingdom.

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The current article represents a set of preliminary observations in the investigation of the mechanisms underlying type-1 diabetic heart disease with primary reference to alterations in histological features of the myocardium and assessments of contractile function in streptozotocin (STZ)-treated type 1 diabetic male Wistar rats compared to age-matched controls. 6-8 weeks following STZ-administration (40 mg/kg), ventricular action potentials were measured in the isolated, spontaneously beating Langendorff perfused rat heart. Contraction and [Ca2+]i transients were measured in electrically stimulated ventricular myocytes by a Video Edge Detection system.At time points of 6-8 and 15 weeks,isolated ventricular tissue was processed for quantitative assessment of fibrosis, measurements of capillary density, myocyte diameter and myofiber to capillary ratio using routine staining techniques. Measurements of ventricular action potential indicated that heart rate (calculated in beats/minute) was significantly reduced (P<0.05, students t test) in the STZ-treated rats (174±13 bpm, n=6) compared to controls (238±12 bpm, n=5).The amplitude of contraction (as a percentage of resting cell length) was significantly greater (P<0.05, students independent samples t test) in STZ-induced diabetic myocytes (5.3±0.23% n=35) compared to age matched controls (3.67±0.5%, n=33). The amplitude and time to peak of Ca2+ transients were not significantly altered (P>0.05, students t test) in the STZ treated myocytes whereas decay of the Ca2+ transient was significantly longer (P<0.05, students t test) in myocytes from STZ-treated (67±3 milliseconds, n=16) compared to control rats (52.8 ± 12 milliseconds, n=20). Visual analysis of stained sections did not reveal any major abnormalities at 6-8 weeks following STZ-administration in control vs. STZ-treated groups compared to the marked structural alterations evident in the 15 week STZ-treated right and left ventricle sections presenting as focal scarring, hypertrophied cardiomyocytes, myofibrillar loss, vacuolisation and large clusters of cells showing end stage apoptosis. Morphometric analysis undertaken in 25 fields for each parameter indicated a modest reactive hypertrophy, reductions in capillary area fraction, significant reduction in capillary to myofiber ratio (1.03±2.6 vs. 0.74±5 ratio units) and a significant increment in collagen area fraction at 15 weeks of treatment (12.75±0.33%) compared to age-matched controls (5.14±18%) and 6-8 week STZ-treated rats (7.99±0.91%). (P<0.05, students t test).The results indicate that STZ-induced type 1 diabetes mellitus results in the development of a cardiomyopathic phenotype characterised by functional abnormalities manifesting as impaired Ca2+ homeostasis and contractility that appear to precede the development of histopathological changes.



Where applicable, experiments conform with Society ethical requirements.

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