Table 1.
Model | GC | Timing of Exposure | Route & Duration of Exposure | Age of Analysis | Cardiac Effects | Cardiomyocyte Characteristics | Ref. |
---|---|---|---|---|---|---|---|
Baboon | BETA | Mid–Late (0.6, 0.64, & 0.68 gestation) | IM; 3 courses of 2 doses | Adult (10 y) | ↑ mid-ventricular pericardial fat thickness; ↔ body weight | N/A | [99] |
Sheep | DEX | Early (27 d GA) | IV; 2 d | Adult (7 y) | ↑ LV wall mass; ↑ LV type I collagen content; ↓ cardiac functional reserve; ↑ blood pressure | N/A | [101] |
Sheep | DEX | Early (40–42 d GA) | IM; 4 doses over 48 h | Fetal (range: 49–142 d GA), Pubescent (7 m) | ↔ heart weight; ↔ heart: body weight ratio | N/A | [94] |
Sheep | BETA | Late (104–118 d GA) | IM; 1 every 7 d (up to 3 doses) | Fetal (range: 109–145 d GA), Pubescent (6 or 12 w) | ↓ heart weight (at 122 & 132 d GA) when exposed to three doses (at 104, 111, & 118 d GA) | N/A | [94] |
Sheep | HC | Late (118–123 d GA) | IV; 10 d | Fetal (129–132 d GA) | ↑ heart weight; ↑ LV & RV wall thickness; ↔ interstitial collagen content; ↔ blood pressure | N/A | [102] |
Sheep | HC | Late (~126–127 d GA) | IV; 2–3 d | Fetal (128–130 d GA) | ↔ heart, LV, RV & IVS weight; ↑ heart: body weight ratio; ↑ LV: body weight ratio; ↑ RV: body weight ratio; ↑ mean arterial pressure; ↑ systolic & diastolic blood pressure | ↔ nuclearity; ↔ number; ↑ LV mononucleated volume; ↓ LV multinucleated volume; ↔ RV volume; | [97] |
Sheep | HC | Late (118–123 d GA) | IV; 10 d | Fetal (129–132 d GA) | N/A | ↑ KI67 positive nuclei; ↑ apoptosis | [103] |
Sheep | HC | Late (~126–128 d GA) | IC; 7 d. IV; 2 d | Fetal (134 d GA) | ↑ heart weight; ↑ heart: body weight ratio | ↑ KI67 positive nuclei; ↔ binucleation; ↔ length; ↔ width | [95] |
Sheep | HC | Late (119 d GA) | IV; 10 d | Fetal (128 d GA) | ↔ heart weight; ↑ heart: body weight ratio; ↑ LV & RV wall thickness; ↑ mean arterial pressure | N/A | [96] |
Sheep | HC | Late (~121–124 d GA) | IV; 5 d | Fetal (125–130 d GA) | ↑ expression of sodium channels & subunits | N/A | [104] |
Sheep | BETA | Late (~115–120 d GA) | IM; 2 doses over 48 h | Fetal (117–123 d GA) | ↑ heart: body weight ratio; ↔ basal contractile LV or RV function; ↑ LV responsiveness to β-adrenoceptor activation | N/A | [105] |
Pig | BETA | Late (91–92 d GA) | IM; 2 doses over 48 h | Fetal (91–92 d GA) | ↔ heart weight; ↔ heart: body weight ratio; ↑ atria weight; ↑ LV free wall weight (females only) | ↓ KI67 positive nuclei; ↑ apoptosis; ↑ LV binucleation; ↔ volume | [98,100] |
Rat | DEX | Late (17 d PC) | SC; 4–5 d | Neonatal (1 d) | ↑ heart: body weight ratio; ↓ myocardial extracellular matrix | ↑ proliferative index | [93] |
Rat | DEX | Late (15–21 d PC) | SC | Fetal (21 d PC) to Adulthood (up to 24 w) | ↓ calreticulin protein expression (fetal); ↑ calsequestrin protein expression (fetal); ↑ calreticulin protein expression (adulthood) | N/A | [106] |
Mice | GR KO | Fetal | N/A | Fetal (E 17.5 d) | ↓ heart size; ↓ ventricular volume; impaired cardiac function; short, disorganized myofibrils; myofibrils fail to align in the myocardium | N/A | [92] |
Neonatal mouse CM | CORT | Treated for 24 h | In vitro | Fetal | N/A | ↑ contractility; ↑ Z-disc assembly; ↑ sarcomere length; ↑ appearance of mature myofibrils; ↑ mitochondrial activity; ↑ contraction & relaxation events | [91] |
BETA, betamethasone; CM, cardiomyocyte; CORT, corticosterone; d, day; d GA, days of gestational age; d PC, days post-conception; DEX, dexamethasone; E, embryonic; GC, glucocorticoid; GR KO, glucocorticoid receptor knockout; h, hours; HC, hydrocortisone; IC, intracoronary; IM, intramuscular; IV, intravenous; IVS, interventricular septum; LV, left ventricle; m, months; N/A, not applicable; RV, right ventricle; SC, subcutaneous; w, weeks; y, years; ↑, increase; ↓, decrease; ↔, no change.