Changes in cardiac performance and sympathetic stimulation during and after fractionated radiotherapy in a rat model.
The consequences of fractionated irradiation on the number of cardiac alpha- and beta-adrenergic receptors, myocardial norepinephrine concentration and in vitro assessed heart function were studied in Sprague-Dawley rats. Animals were locally irradiated on the thorax with a total dose of 50 Gy, in 5 weeks, using two different fractionation schemes (5 x 2.0 Gy/week and 3 x 3.3 Gy/week). Functional and biochemical assays were performed during treatment and at 6 months after initiation of treatment. During fractionated irradiation, the numbers of alpha- and beta-adrenergic receptors tended to rise. During this period, myocardial norepinephrine concentration remained fairly constant and no decrease in cardiac output was observed. At 6 months, a significant increase of the numbers of alpha- and beta-adrenergic receptors was observed in the 3.3 Gy/fraction group compared to age-matched controls, p = 0.012 and p = 0.02, respectively. At this time point, the myocardial norepinephrine concentration had decreased below control levels (p = 0.008 for the 3.3. Gy/fraction schedule, and p = 0.03 for the 2.0 Gy/fraction schedule). At 6 months, the cardiac output declined to 61% (p = 0.009) and 69% (p = 0.04) of control values for the 3.3 and 2.0 Gy/fraction schedules, respectively. The present data clearly show development of late cardiac sequelae caused by fractionated thorax irradiation with a total dose of 50 Gy. Moreover, this study lends support to the importance of fraction size with regard to the severity of the radiation-induced cardiac damage.
Wondergem
J
J
Department of Clinical Oncology, University Hospital Leiden, Netherlands.
Franken
N A
NA
van der Laarse
A
A
Persons
C C
CC
Van Ravels
F J
FJ
Reijnart
I C
IC
Strootman
E G
EG
D000818:Animals; D002302:Cardiac Output / Q000528:radiation effects; D002303:Cardiac Output, Low / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000528:radiation effects*; D009206:Myocardium / Q000737:chemistry; D009638:Norepinephrine / Q000032:analysis / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects; D011879:Radiotherapy Dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000528:radiation effects; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000528:radiation effects; D013564:Sympathetic Nervous System / Q000528:radiation effects*; D013909:Thorax / Q000528:radiation effects
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009638:Norepinephrine