No abstract

CFR is impaired in subjects with prehypertension, but this impairment is not as severe as that in hypertension.

Cyclophosphamide (CP) is an antineoplastic agent used alone or in combination with other chemotherapeutic agents for the treatment of many neoplastic diseases. Hemorrhagic cystitis (HC) is a major potential toxicity and dose limiting side effect of CP. Recently, it has been shown that endogenous inflammatory mediators are involved in cystitis by increasing nitric oxide (NO) production in target tissue. The aim of this study was to evaluate the relationship between NO and CP induced hemorrhagic cystitis HC in rats. A total of 30 female Spraque-Dawley rats were divided into 4 groups. Group 1 served as control, three groups received single dose of CP (100 mg/kg) intraperitoneally (i.p.): group 2 received CP only. Group 3 received the NO precursor L-arginine (80 mg/kg/day), and group 4 received the selective inducible NO synthase (iNOS) inhibitor S-methylisothiourea (SMT; 20 mg/kg/day) before and the day after cyclophosphamide injection. CP injection resulted in severe cystitis. SMT but not L-arginine produced marked inhibition of CP induced bladder damage. We concluded that NO produced by iNOS, is an important mediator in the pathogenesis of CP induced cystitis.

Oxidants may be important in the pathogenesis of CP-induced cystitis. Melatonin and alpha-tocopherol may help to ameliorate bladder damage along with other drugs such as mesna and diuretics.

Background: Coronary flow reserve (CFR) reflects the functional capacity of microcirculation to adapt to blood demand during increased cardiac work. In this study, CFR of hemodialysis patients with angiographically normal coronary arteries was evaluated using transthoracic second harmonic Doppler echocardiography. Methods and Results: Ten hemodialysis patients, and 14 sex-, age- and left ventricular mass index-matched hypertensive controls with angiographically normal coronary arteries underwent transthoracic second harmonic Doppler echocardiographic examination. Coronary basal diastolic peak flow velocities and hyperemic peak flow velocities after dipyridamole infusion (0.56 mg/kg over 4 min) were measured. CFR was defined as the ratio of hyperemic to basal diastolic peak velocities. CFR ≧2.0 was regarded as normal. Additionally, Doppler tissue imaging pulse wave measurements were taken from the lateral and septal corners of the mitral annulus. CFR values were significantly lower in the study group than in the control group (2.03 ± 0.3 vs. 2.61 ± 0.5, p = 0.005). In 5 of 10 hemodialysis patients, CFR was <2.0 (50%), however in only 1 of 14 control patients it was <2.0 (5%). Conclusions: Impairment of coronary microvasculature occurs earlier in patients with chronic renal failure and may be the harbinger of subsequent primary uremic myocardial disease. In patients with chronic renal failure and normal coronary arteries, decreased CFR by transthoracic echocardiography might be regarded as an early finding of an affected coronary vasculature.