Trifunovic B, Woodiwiss A J, Duffield M, Norton G R
Department of Physiology, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Can J Physiol Pharmacol. 1998 Jun;76(6):657-64. doi: 10.1139/cjpp-76-6-657.
Although cardiac early and mid-diastolic stiffness constants are well accepted as being modulated by alterations in myocyte active processes, increments in left ventricular end diastolic (LVED) stiffness (LVED k; g x cm(-2)) in classical pathological models of a reduced LVED k (e.g., diabetes mellitus (DM) and hypertension) are determined largely by the properties of the myocardial extracellular matrix (ECM). As such, increases in LVED k in the latter cardiac pathologies are insensitive to acute changes in cardiac load, heart rate, and contractility. We examined whether the same attributes that apply to changes in LVED k in DM and in spontaneously hypertensive rats (SHRs) also apply to an androgenic steroid (nandrolone decanoate; 5 mg x kg(-1) biweekly) induced increase in LVED k. Myocardial collagen (ECM) characteristics and the capacity of acute verapamil-mediated changes in cardiac dynamics to impact on LVED k were evaluated after 3 months of steroid treatment to rats, 4 months of DM in rats, and in 45-week-old SHRs. Chronic steroid administration increased LVED k (steroid = 42 +/- 4, control = 25 +/- 2; p < 0.01). An acute infusion of verapamil to steroid-treated rats decreased LVED k to values not different from controls (29 +/- 3; p < 0.05 as compared with LVED k at baseline). Measures of myocardial collagen concentrations, phenotype ratios, and cross-linking were unchanged following steroid administration. Verapamil failed to alter the increased LVED k that occurs in either rats with DM or in SHRs, despite similar effects on cardiac dynamics as those noted in steroid-treated rats. The increased LVED k in the former animal models was associated with alterations in the ECM. In conclusion, the unique lack of association of the androgenic steroid-induced increase in LVED k with alterations in the myocardial ECM and the novel sensitivity of the steroid-mediated increment in LVED k to acute alterations in cardiac dynamics further supports the notion that changes in LVED k should not be considered to be a reflection of ECM characteristics in all cardiac conditions.
尽管心脏舒张早期和中期的僵硬度常数被广泛认为受心肌细胞活性过程改变的调节，但在左心室舒张末期（LVED）僵硬度降低（LVED k；g×cm⁻²）的经典病理模型（如糖尿病（DM）和高血压）中，LVED僵硬度（LVED k）的增加很大程度上由心肌细胞外基质（ECM）的特性决定。因此，在后者的心脏病变中，LVED k的增加对心脏负荷、心率和收缩性的急性变化不敏感。我们研究了适用于DM和自发性高血压大鼠（SHR）中LVED k变化的相同属性是否也适用于雄激素类固醇（癸酸诺龙；每两周5mg×kg⁻¹）诱导的LVED k增加。在对大鼠进行3个月的类固醇治疗、对大鼠进行4个月的DM诱导以及对45周龄的SHR进行相应处理后，评估心肌胶原（ECM）特征以及急性维拉帕米介导的心脏动力学变化对LVED k的影响能力。长期给予类固醇会增加LVED k（类固醇组 = 42±4，对照组 = 25±2；p < 0.01）。对接受类固醇治疗的大鼠急性输注维拉帕米可使LVED k降至与对照组无差异的值（29±3；与基线时的LVED k相比，p < 0.05）。给予类固醇后，心肌胶原浓度、表型比例和交联的测量值均未改变。尽管维拉帕米对心脏动力学的影响与在接受类固醇治疗的大鼠中观察到的相似，但它未能改变DM大鼠或SHR中出现的LVED k增加。在前者的动物模型中，LVED k增加与ECM改变有关。总之，雄激素类固醇诱导的LVED k增加与心肌ECM改变之间独特的缺乏关联，以及类固醇介导的LVED k增加对心脏动力学急性变化的新敏感性，进一步支持了这样一种观点，即在所有心脏状况下，LVED k的变化不应被视为ECM特征的反映。
