Ultrastructural and functional effects of lead poisoning on adult canine myocardium : assessment of thiamin treatment

The effects of lead (Pb) poisoning on the adult canine myocardium were assessed quantitatively using stereological techniques, functional testing, and blood analyses as well as qualitatively by morphological investigation. Subacute (chronic, but lethal) lead poisoning was studied in fifteen adult dogs divided into three groups: control, Pb treated (Pb given in ascending amounts from 50 mg/kg to 200 mg/kg Pb per day for up to 9 weeks) and Pb + B₁ vitamin treated (Pb given as described above and thiamin given at a dose of 100 mg/kg i.m. daily). Relative measurements using stereological techniques compared the volume fractions of cellular components of the three groups. Blood was analyzed for lead, hemoglobin, hematocrit, total erythrocytes, total leukocytes, thiamin pyrophosphate (TPP), delta-aminolevulinic acid dehydratase activity (ALAD), and zinc protoporphyrin (ZPP). The major finding of the stereological analysis was the statistically significant increase of 3.2% in myofilament volume in the Pb treated group and the significant decrease in mitochondrial volume in both the Pb treated and Pb + B₁ treated groups. A statistically significant decrease in the mitochondria/myofilament volume ratio was found in the Pb treated, but not Pb + B₁ treated group. This may indicate either a protective effect of thiamin on mitochondria or a reduced compensatory need of the myocyte to increase myofilament volume. Control values for mitochondrial and myofilament volumes were consistent with published reports on canine left ventricular myocardium. Electron microscopic observations alone showed no morphological differences in mitochondria or other cellular components between treatment groups. A trend toward decreased function was noted only in the Pb treated group by a decrease in the first derivative of ventricular pressure (dp/dt at 50 mmHg developed isovolumic pressure) and by a decrease in peak ventricular pressure. Thiamin had little effect on the animals' clinical status. Tissue and blood lead levels did not indicate a protective effect of thiamin. TPP levels were found to significantly increase in Pb treated animals and rise even higher in Pb + B₁ treated animals. In dogs from both lead treated groups, ALAD activity decreased to less than 10% of initial values and ZPP levels increased slightly.