A B S T R A C T To evaluate the effect of Ca"+ on renin release, plasma renin activity (PRA) was measured after acute and chronic Ca"+ administration. 1% CaCl2 was infused into one renal artery of 10 anesthetized dogs (0.3 mg/kg/min). The excreted fraction of filtered calcium (EFc,++) and EFN.+ from the infused kidney were elevated (P <0.04) during three successive 15-min infusion periods. Serum calcium concentration was significantly elevated (P < 0.001). Creatinine clearance, systemic arterial pressure, and renal blood flow did not change (P> 0.10). Compared to control (45 ng/ ml/h+5.2 SE), renal venous PRA was suppressed (P < 0.0001) after infusion of Ca`+ for 15, 30, and 45 min (20 ng/ml/h±4.6, 16 ng/ml/h+4.0, and 13 ng/ml/h +2.7, respectively). 15 and 30-min after infusion, PRA did not differ from control (P > 0.20). Chronic Ca++ loading was achieved in Sprague-Dawley rats by replacing drinking water with 1% CaCla for 17 days. At sacrifice, serum Cae+, Nae, and K+ of controls (n = 12) did not differ (P > 0.60) from Cae+-loaded rats (n = 12). Cae+ excretion (467 Aeq/24 h±51) was elevated (P < 0.001) compared to controls (85 aeq/24 h±12). PRA (8.6 ng/ml/h± 1.4) and renal renin content of Ca++-loaded rats did not differ from controls (P > 0.80). However, after 8 days of sodium deprivation, both PRA and renal renin content of calcium-loaded animals were significantly lower than the respective values in pair-fed controls (P < 0.005). During the period of sodium deprivation, calcium-drinking animals were in greater negative sodium balance than controls (P < 0.005). The data are consistent with the hypothesis that acute and chronic calcium administration inhibit renin secretion. INTRODUCTIONSodium load within the macula densa and pressure or stretch in the renal afferent arteriole are two wellstudied factors involved in the regulation of renin secretion (1). Recently, it has been demonstrated that potassium balance also affects renin release (2-6), possibly by altering the load of filtered sodium presented to the distal segment of the nephron (7-9). Acute calcium infusion in the dog decreases the fraction of filtered sodium reabsorbed and results in a natruresis (10). Furthermore, during acute hypercalcemia in the dog, Suki, Eknoyan, Rector, and Seldin demonstrated decreased sodium reabsorption in the ascending limb of the loop of Henle (11). Consequently, the acute infusion of calcium not only results in increased sodium excretion, but also increases the amount of filtered sodium presented to the distal segment of the nephron. If potassium-induced renin inhibition were mediated by an effect on proximal sodium reabsorption, calcium infusion might likewise be expected to inhibit renin secretion. To evaluate this hypothesis, a series of experiments was undertaken to measure the in vivo effects of acute and chronic calcium administration on renin activity. In the acute studies, calcium chloride was infused directly into the renal artery of anesthetized dogs. Chronic calcium loading in the rat was achieved by the ad...

ObjectiveThroughout the UK, hypothermic static storage of organs prior to reperfusion and transplantation is the preferred method of preservation. The rationale behind this is the simplicity, cost-effectiveness, portability and proven good allograft results using such methods [1,2]. Whilst the cold environment slows metabolism, anaerobic metabolism continues to occur, albeit at a slower rate, the end-products of which contribute to the generation of oxygen free radicals and hence ischaemia-reperfusion injury. It is known that cellular oedema and functional impairment develop during anaerobic cold storage, the extent of which is related to the length of storage and the composition of the preservation solution used [3][4][5]. Cold storage does not allow assessment of viability markers as it renders metabolic studies difficult to interpret. Thus some marginal organs may be discarded unnecessarily, or transplanted and have primary nonfunction.The expanding mismatch between supply and demand for renal allografts has prompted development of preservation techniques to try and help expand the donor pool and improve allograft function. Normothermic preservation is not a new concept but has seen a recent revival in renewed interest [6][7][8] The potential beneficial roles include maintaining an organ at physiological conditions thus avoiding the harmful effects of an anaerobic environment, viability assessment allowing use of marginal organs and possible ex vivo manipulation.The aim of this study was to assess the viability and function of renal allografts under normothermic conditions using a novel nonphosphate buffered normothermic preservation solution AQIXÒRS-I (Res

A possible interaction between betamethasone and vecuronium was examined in 20 rat phrenic nerve-hemidiaphragm preparations. Ten preparations were bathed in a physiological solution with betamethasone 1 mumol litre-1 added and, after a 30-min period were exposed to vecuronium at concentrations of 4, 6, 8 and 10 mumol litre-1 with vecuronium free washings between each exposure. Ten control experiments were performed also using a betamethasone-free bathing solution. In comparison with control, the betamethasone group had significantly (P = 0.0008) less depression of muscle contraction (twitch) force at all concentrations of vecuronium. The calculated ED50 (50% depression of muscle contraction force) was 5.65 mumol litre-1 for controls and 7.39 mumol litre-1 for betamethasone-pretreated preparations. This study confirms our previous clinical observations that an interaction occurs between vecuronium and betamethasone which is characterized by resistance to neuromuscular block.

Steroids induce resistance to neuromuscular blocking drugs. Betamethasone-induced resistance to vecuronium has been demonstrated in vitro, and a presynaptic site of interaction has been suggested. This study investigated whether atracurium is similarly affected. Rat phrenic nerve-hemidiaphragm preparations were bathed in a physiologic solution, and one-half were exposed to betamethasone (1 mumol/L). Dose responses were recorded for atracurium (8-13 mumol/L) and vecuronium (2-12 mumol/L) for control and betamethasone-treated preparations. In comparison to control, the betamethasone groups had significantly less depression of muscle contraction force at all concentrations of atracurium (P = 0.0004) and vecuronium (P = 0.002). The calculated ED50 (50% depression of muscle contraction force, expressed as mean +/- SEM) for atracurium was 8.83 +/- 0.62 mumol/L for controls and 11.19 +/- 0.54 mumol/L for betamethasone-treated preparations. The calculated ED50 for vecuronium was 4.72 +/- 0.41 mumol/L for controls and 6.84 +/- 0.66 mumol/L for betamethasone-treated preparations. Betamethasone therefore increased the ED50 for atracurium by 27% and vecuronium by 45%; however, the magnitudes of these differences were not significant (P = 0.74) between the neuromuscular blocking agents. These results indicate that betamethasone-induced resistance to nondepolarizing neuromuscular blockade affects both atracurium and vecuronium to similar degrees in vitro.

Porcine DCD hearts after 29 min of warm ischemia can be reanimated using the method described. A mechanism of reoxygenation (oxygenated MP or coronary sinus oxygen persufflation) during preservation appears mandatory for hearts from DCDs. Persufflation was associated with a higher probability of successful reanimation. Dialysis in the warm phase was useful in removing metabolites that could interfere with reanimation. The results demonstrate the potential of DCDs to counter the decline affecting heart transplantation.