OBJECTIVE: Elevated pulmonary vascular resistance and transpulmonary gradient are predictors of increased perioperative mortality in patients undergoing orthotopic heart transplantation. Sodium nitroprusside and prostacyclin PGI2 are routinely used to assess the reversibility of pulmonary vascular resistance and transpulmonary gradient in heart transplant candidates, but their use is limited by their systemic vasodilatory effect. The aim of this study was to evaluate the systemic and pulmonary haemodynamic effects of low concentration (10 and 20 parts per million) inhaled nitric oxide in patients with severe heart failure with elevated transpulmonary gradient and pulmonary vascular resistance undergoing assessment for cardiac transplantation, and to compare the haemodynamic effects of inhaled nitric oxide with those of sodium nitroprusside and prostacyclin PGI2. METHOD: In 10 consecutive patients with elevated transpulmonary gradient (16+/-2 mm Hg) and pulmonary vascular resistance (3.6 +/-0.3 Wood units (WU)) nitric oxide (10 and 20 parts per million in 23% inspired oxygen (O2) via a tight fitting facemask) and increasing doses of intravenous sodium nitroprusside and prostacyclin were administered in a random, single-blinded fashion. RESULTS: Inhalation of nitric oxide (10 ppm) reduced the transpulmonary gradient (-7+/-2 mm Hg; P<0.01) and pulmonary vascular resistance (-1.8+/-0.4 WU; P<0.001) but did not affect the systemic vascular resistance (-0.3+/-1 WU) or mean systemic arterial pressure (-1.3 5 mm Hg). Sodium nitroprusside and prostacyclin reduced the transpulmonary gradient (-4.5+/-2 mm Hg; P<0.01 and -3.6+/-2 mm Hg; P<0.05), pulmonary vascular resistance (-1.5+/-0.4 WU; P<0.001 and -1.3+/-0.4 WU; P<0.01), systemic vascular resistance (-7+/-2 WU; P<0.01 and -7.2+/-2 WU; P<0.01) and mean systemic arterial pressure (-15+/-5 mm Hg; P<0.01 and -18+/-4 mm Hg; P<0.01). CONCLUSION: Low-concentration inhaled nitric oxide is as effective as sodium nitroprusside and prostacyclin in reducing transpulmonary gradient and pulmonary vascular resistance, and is highly pulmonary vasoselective.

Administration, Inhalation↗

PubMed1996

Stability of amoxicillin-clavulanate in BACTEC medium determined by high-performance liquid chromatography and bioassay.

The stabilities of amoxicillin (16 micrograms/ml) and clavulanate (8 micrograms/ml), alone and in combination in BACTEC medium (Middlebrook 7H12B medium), were determined by high-performance liquid chromatography (HPLC) and bioassay. By HPLC, the half-life of amoxicillin (trihydrate and sodium) in combination with clavulanate in nonradiolabelled 7H12B medium was 6.7 days, whereas the half-life of clavulanate in combination with amoxicillin was 2.0 days. By bioassay, the half-lives of amoxicillin trihydrate and clavulanate in radiolabelled 7H12B medium were comparable (7 and 2 days, respectively) to those determined by HPLC. When clavulanate was tested alone, the half-life was determined to be 1.88 days by HPLC and 1.87 days by bioassay. The relatively short half-life of clavulanate can be adjusted by a procedure of "topping up," or adding one-half the concentration of clavulanate every second day, in order to allow accurate amoxicillin-clavulanate MIC testing with the BACTEC mycobacterial susceptibility system.

Amoxicillin↗

PubMed1996

A 12-lipoxygenase product, 12-hydroxyeicosatetraenoic acid, is increased in diabetics with incipient and early renal disease.

Earlier studies in diabetic animal models or ex vivo from diabetics suggest a deficiency in prostacyclin (PGI2) production and an increase in an alternate arachidonic acid metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), which stimulates angiogenesis, mitogenesis, and inhibits renin secretion. We studied the urinary excretion rate of 6-keto-PGF1 alpha (a stable metabolite of PGI2) and 12-HETE in controls and 42 noninsulin-dependent diabetes mellitus (NIDDM) patients with normal renal function and those with micro- or macroalbuminuria/hyporeninemic hypoaldosteronism (HH). The 2 eicosanoids were measured in urine using previously described high pressure liquid chromatography and RIA methods. Normal subjects and patients with NIDDM and microalbuminuria were infused with low dose calcium infusions that stimulate prostacyclin production in normal subjects. The PGI2 excretion rate of NIDDM patients with normal renal function was not different from that of controls (143 +/- 17 vs. 118 +/- 34 ng/g creatinine), but was reduced in those with microalbuminuria (75 +/- 10) and in macroalbuminuria patients (48 +/- 7; P < 0.01). In contrast, 12-HETE was increased in diabetics with normal renal function as well as in those with micro- or macroalbuminuria patients (69 +/- 18 vs. 250 +/- 62 vs. 226 +/- 60 and 404 +/- 131 ng/g creatinine; P < 0.01). Calcium did not stimulate PGI2, but increased 12-HETE in diabetics with microalbuminuria in contrast to levels in normal subjects. HH patients excreted less PGI2 (as previously reported), but had increased 12-HETE. HETE/PGI2 ratios further demonstrated these changes in the various groups. In a nondiabetic hypertensive microalbuminuria group, 12-HETE excretion was normal (73 +/- 28 ng/g creatinine). We conclude that the lipoxygenase product 12-HETE is increased early in the diabetic process, whereas PGI2 production is progressively impaired in NIDDM. These changes may play a role in the vascular disease of diabetes and partially explain the HH syndrome.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1996

Ouabain is a potent inhibitor of aldosterone secretion and angiotensin action in the human adrenal.

Digitalis glycosides and a putative ouabain-like substance act by inhibiting Na,K-adenosine triphosphatases and could regulate aldosterone secretion. We studied the effects of ouabain on basal and angiotensin II (AII)-induced aldosterone in rat and human adrenal glomerulosa cells. In the rat, ouabain at doses as high as 10(-4) mol/L had no effect on basal aldosterone secretion, but caused a dose-related inhibition of AII and ACTH secretion. In human glomerulosa cells, ouabain was 1000 times more potent on both basal and AII stimulation, with action at 10(-8) mol/L. The effect of ACTH was also blunted by 10(-8)-10(-7) mol/L ouabain. However, the effect of potassium (8.7 mmol/L) on aldosterone was not altered by these doses of ouabain. These results suggest that nanomolar levels of ouabain can reduce aldosterone secretion from human zona glomerulosa cells.

Adrenal Glands↗