Caidahl K, Edén S, Bengtsson B A
Department of Clinical Physiology, Sahlgren's University Hospital, Gothenburg, Sweden.
Clin Endocrinol (Oxf). 1994 Mar;40(3):393-400. doi: 10.1111/j.1365-2265.1994.tb03937.x.
With the advent of recombinant human GH (rhGH), it has become possible in controlled clinical studies to explore the effects of GH replacement in adults with GH deficiency. The objective of this study was to determine cardiovascular and renal effects of GH replacement in adults with GH deficiency.
We studied ten patients (one woman and nine men), mean age 47 years, with GH deficiency.
The patients were given s.c. rhGH (Humatrope, Eli Lilly) 0.5 U/kg/week or placebo in a 6-month double blind cross-over study. Cardiac and renal function was measured before drug administration (baseline), before cross-over (i.e. after 6 months), and before termination of drug administration (after another 6 months). Analysis of variance was used to compare measurements during GH replacement with baseline and placebo measurements. One patient was excluded because of atrial fibrillation.
Main outcome measures were glomerular filtration rate and Doppler-echocardiographic estimates of cardiac function and structure. Computerized exercise electrocardiogram, spirometry, and blood samples for analyses of plasma hormones were also obtained.
Left ventricular function was maintained during GH replacement. However, left ventricular mass increased from 211 to 249 g (P < 0.05) mainly due to increased left ventricular dimension since wall thicknesses did not increase. The left atrium increased from 38 to 41 mm (P < 0.05), possibly because stroke volume increased from 92 to 118 ml (P < 0.0001) and cardiac output increased from 5.29 to 7.58 l/min (P < 0.05). Total peripheral resistance decreased from 18.9 to 12.4 mmHg min/l (P < 0.05), and diastolic blood pressure from 79 to 72 mmHg (P < 0.05). Heart rate at rest increased from 58 to 70 beats/min. Systolic blood pressure at rest was unchanged, as was systolic blood pressure during dynamic exercise. GH replacement did not cause ST-abnormalities. Serum creatinine decreased from 91.4 to 85.3 mumol/l (P < 0.05) and glomerular filtration rate increased from 89.6 to 99.8 ml/min (P < 0.01).
Thus, GH replacement has favourable cardiovascular and renal effects including increase of stroke volume and glomerular filtration rate with reduction of peripheral resistance.
随着重组人生长激素(rhGH)的出现,在对照临床研究中探索生长激素替代疗法对成年生长激素缺乏患者的影响已成为可能。本研究的目的是确定生长激素替代疗法对成年生长激素缺乏患者心血管和肾脏的影响。
我们研究了10例生长激素缺乏患者(1名女性和9名男性),平均年龄47岁。
在一项为期6个月的双盲交叉研究中,患者皮下注射rhGH(优猛茁,礼来公司)0.5 U/kg/周或安慰剂。在给药前(基线)、交叉前(即6个月后)以及给药结束前(再过6个月)测量心脏和肾脏功能。采用方差分析比较生长激素替代治疗期间的测量值与基线值和安慰剂测量值。一名患者因房颤被排除。
主要观察指标为肾小球滤过率以及心脏功能和结构的多普勒超声心动图评估。还进行了计算机化运动心电图、肺功能测定,并采集血样分析血浆激素。
生长激素替代治疗期间左心室功能得以维持。然而,左心室质量从211克增加至249克(P<0.05),主要是由于左心室内径增加,因为室壁厚度并未增加。左心房从38毫米增加至41毫米(P<0.05),可能是因为每搏输出量从92毫升增加至118毫升(P<0.0001),心输出量从5.29升/分钟增加至7.58升/分钟(P<0.05)。总外周阻力从18.9降至12.4 mmHg·min/l(P<0.05),舒张压从79 mmHg降至72 mmHg(P<0.05)。静息心率从58次/分钟增加至70次/分钟。静息收缩压未改变,动态运动时的收缩压也未改变。生长激素替代治疗未导致ST段异常。血清肌酐从91.4降至85.3 μmol/l(P<0.05),肾小球滤过率从89.6升至99.8 ml/min(P<0.01)。
因此,生长激素替代疗法具有有利的心血管和肾脏效应,包括增加每搏输出量和肾小球滤过率以及降低外周阻力。