Cardioinotropic Effects in Subchronic Intoxication of Rats with Lead and/or Cadmium Oxide Nanoparticles

Figure 1. Examples of isobolograms illustrating variations in the type of combined action produced by CdO–NP and PbO–NP on the indices: (a) thrombocrit (prevailing single-factor action of PbO–NP, changing to additivity at low doses and to opposite action at high doses), (b) eosinophil count (prevailing single-factor action of CdO–NP), (c) SH–groups (additivity, changing to subadditivity at high NP doses), (d) liver mass (additivity at low NP doses, changing to antagonism at high NP doses), (e) acaryotic hepatocytes (additivity), (f) coefficient of genomic DNA fragmentation (superadditivity). The axes plot NP doses in mg/kg; numbers on the isoboles show the magnitude of the corresponding effect. The response ranges are distinguished by different colors.

Figure 2. Representative examples of electrophoregrams showing the location of α– and β–myosin heavy chains (MHC) recovered from the myocardium of rats. Left to right: control, group after exposure to PbO–NP, after exposure to CdO–NP, after combined exposure to PbO–NP and CdO–NP, and after combined exposure against oral bioprophylactic complex (BPC) administration.

Figure 3. The relationships of the amplitude of active tension (A) and passive tension (B) vs. relative muscle length, obtained for trabeculae (left panels) and papillary muscles (right panels) of the control, PbO–NP and CdO–NP groups. Muscle length is shown in LMAX units. Data are shown as mean ± s.e. There are significant differences: *—CdO–NP vs. Control, ^—CdO–NP + PbO–NP vs. PbO–NP, ○—PbO–NP vs. CdO–NP (p < 0.05).

Figure 4. The relationships of the maximal normalized rate (A), time-to-peak of force development (B) and time of relaxation to 50% amplitude of tension (C) vs. relative muscle length, obtained for trabeculae (left panels) and papillary muscles (right panels). Muscle length is shown in LMAX units. Data are shown as mean ± S.E. There are significant differences: *—CdO–NP vs. Control, +—PbO–NP vs. Control, #—CdO–NP + PbO–NP vs. Control, ●—CdO–NP + PbO–NP vs. CdO–NP, ^—CdO–NP + PbO–NP vs. PbO–NP, ○—PbO–NP vs. CdO–NP (p < 0.05).

Figure 5. The force–velocity relationships of isolated trabeculae (left panel) and papillary muscles (right panel). Velocity is shown in relative units according to muscle’s working length. Data are shown as mean ± s.e. There are significant differences: #—CdO–NP + PbO–NP vs. Control, ^—CdO–NP + PbO–NP vs. PbO–NP, ●—CdO–NP + PbO–NP vs. CdO–NP (p < 0.05).

Figure 6. Representative examples of the length–tension loops obtained for isolated trabeculae (left panel) and papillary muscles (right panel). Data are shown as mean ± s.e. Statistical analysis was carried out for work values calculated using the data on length–tension loops.

Figure 7. The end–systolic length–afterload relationships of isolated trabeculae (left panel) and papillary muscles (right panel). Data are shown as mean ± s.e. There are significant differences: #—CdO–NP + PbO–NP vs. Control, ^—CdO–NP + PbO–NP vs. PbO–NP NP (p < 0.05, Mann–Whitney U-test).

Figure 8. The work–afterload relationships of isolated right ventricular trabeculae (left panel) and papillary muscles (right panel) in the control, PbO–NP, and CdO–NP groups. Data are shown as mean ± S.E. There are significant differences: *—CdO–NP vs. Control, +—PbO–NP vs. Control, #—CdO–NP + PbO–NP vs. Control, ●—CdO–NP + PbO–NP vs. CdO–NP, ^—CdO–NP + PbO–NP vs. PbO–NP, ○—PbO–NP vs. CdO–NP (p < 0.05, Mann–Whitney U-test).

Figure 9. The relationship between post-rest potentiation (assessed as ratio between the amplitudes of the first twitch after 30 s rest and the pre-rest twitch) and pacing rate, obtained for isolated trabeculae (left panel) and papillary muscles (right panel). The pacing rate is varied between 1 and 3 Hz. The muscles are paced at 0.95 LMAX. Data are shown as mean ± S.E. There are significant differences: +—PbO–NP vs. Control, ●—CdO–NP + PbO–NP vs. CdO–NP, ^—CdO–NP + PbO–NP vs. PbO–NP (p < 0.05, Mann–Whitney U-test).

Figure 10. Examples of isobolgrams illustrating variations in the type of combined action produced by CdO and PbO nanoparticles on myocardial contractility: (a) active tension in trabeculae at L = LMAX (single-factor action of cadmium, changing to contradirectionality at high doses), (b) active tension in papillary muscles at L = LMAX (from additivity at low doses through single-factor action of cadmium at low doses of lead to contradirectionality at high NP doses), (c) passive tension in trabeculae at L = LMAX (superadditivity), (d) maximal normalized rate in papillary muscles at L = 0.9LMAX (opposite actions), (e) force–velocity relationships in trabeculae at P = 0.7P0 (complex picture from contradirectionality at low doses to additivity at high NP doses), (f) maximal shortening velocity of papillary muscles at P = 0.8P0 (additivity, changing to subadditivity). The axes plot doses as fractions of actual value; numbers on the isoboles indicate the level of the corresponding effect).