Capillary growth in anemia-induced ventricular wall remodeling in the rat heart.

Abstract

To determine whether anemia-induced cardiac hypertrophy affects ventricular size and shape and the component structures of the capillary network of the left and right ventricles, young male rats were fed an iron- and copper-deficient diet for 7 weeks. By that time, blood hemoglobin content fell to 5 +/- 1 g/dl, and packed cell volume fell to 18 +/- 3%. To further characterize the implications of anemia, red blood cell number, hemoglobin corpuscular content, systemic arterial pressure, heart rate, and blood viscosity were measured. Moreover, the changes in ventricular weights were analyzed in terms of the alterations in ventricular wall area and ventricular wall thickness to establish the impact of the elevation in load associated with a high cardiac output state on ventricular remodeling. The quantitative properties of the capillary circulation were also examined biventricularly by low power electron microscopic morphometry to evaluate the adaptive growth potential of the coronary microcirculation in this form of cardiac hypertrophy. Anemia was found to interfere with the production of red blood cells and their mean corpuscular hemoglobin content and resulted in a 40% reduction in blood viscosity and a 12% and 27% decrease in systolic and diastolic blood pressure, respectively. The changes in heart rate were not statistically significant. In comparison with control animals, heart weight increased by 50%, but the enlargement in right ventricular mass (65%) was greater than that of the left ventricle (47%). Ventricular hypertrophy occurred with increases in wall area and wall thickness although the former increased consistently more than the latter in either ventricle. Tissue growth was accompanied by a 60% lengthening of the capillary network, which in combination with an increase in capillary diameter resulted in a 65% and 34% expansion in capillary luminal volume and 56% and 20% larger luminal surface density in the left and right sides of the heart, respectively. In conclusion, hypochromic microcytic anemia leads to eccentric ventricular hypertrophy with a significant amount of capillary proliferation that may tend to protect the myocardium from the increased potential for ischemic injury.

Adaptive response of the heart to long-term anemia induced by iron deficiency

“…IDA induces LV eccentric hypertrophy in developing rats (16,21,22,27); however, the molecular mechanism responsible for LV remodeling in this setting has been unknown. Recent studies showed that Epo treatment improves quality-of-life scores and LV ejection fraction in patients with HF (14), indicating that Epo has protective effects on cardiac diseases.…”

“…Thus iron deficiency anemia (IDA) is obviously important not only as a primary cause, but also as a facilitator, of HF. Numerous studies have shown that IDA leads to left ventricular (LV) hypertrophy in developing rats (16,21,22,27), but no data about its molecular mechanisms, including the molecular signaling pathways, of IDAinduced cardiac remodeling, are available.…”

Glycogen Synthase Kinase-3α Reduces Cardiac Growth and Pressure Overload-induced Cardiac Hypertrophy by Inhibition of Extracellular Signal-regulated Kinases

“…The positively stained (red) fibrotic area was expressed as a percentage of total area. Total cardiac myocyte numbers were estimated using a published method (19). Briefly, the number of nuclei per unit area of myocardium (N(n) A ) was determined in 20 fields (40ϫ).…”

Angiostatin Inhibits Coronary Angiogenesis During Impaired Production of Nitric Oxide

“…[23][24][25] VEGF-knockout mice developed ischemic cardiomyopathy because of limited capillary density. 24 Patients with dilated cardiomyopathy and decreased capillary density show decreased VEGF expression.…”