Critical role of the extracorporeal blood temperature in the hemodynamic response during hemofiltration.

Impaired vascular reactivity during combined ultrafiltration-hemodialysis (UF+HD) compared with hemofiltration (HF) remains a rather enigmatic problem, the causes of which are still not well understood. Although a number of factors have been claimed to be responsible, most recent studies point to a major role of the extracorporeal blood temperature, which is usually lower during HF compared with UF + HD. However, previous studies in which hemodynamics were studied during UF + HD and HF in relation to the extracorporeal blood temperature are limited by the use of acetate in UF + HD, and measurements were often confined to BP and heart rate. Therefore, arterial BP, as well as forearm vascular resistance (FVR) and venous tone (strain-gauge plethysmography), was measured in 11 hemodialysis patients during 3 h UF + HD (37.5 degrees C) and predilution HF (39.0 degrees C = warm HF), resulting in equivalent extracorporeal blood temperatures. Patients were also studied during cold HF at an infusate temperature of 36.0 degrees C. UF + HD and HF were matched with respect to the dialysate and infusate composition (bicarbonate), bio-compatibility factors, and small molecule clearance. At equivalent temperatures, UF + HD and HF were associated with a comparable vascular and BP response. Only cold HF was associated with a significant increase in FVR. In addition, FVR and venous tone, as well as arterial BP, were all significantly higher during cold HF compared with both UF + HD and warm HF. These results indicate that the disparity in vascular reactivity between UF + HD and HF is primarily related to differences in the extracorporeal blood temperature.

Acute renal effects of neutral endopeptidase inhibition in humans.

The acute renal effects of neutral endopeptidase 24.11 (E-24.11) inhibition induced by a single oral dose of sinorphan (100 mg) were investigated in 10 healthy normotensive subjects on normal sodium diet. Sinorphan inhibited 90% of E-24.11 activity and increased plasma atrial natriuretic peptide (ANP) and urinary guanosine 3',5'-cyclic monophosphate (cGMP) by 70 and 100%, respectively. Sinorphan increased urinary sodium output by 50% (P < 0.001) and decreased fractional distal reabsorption by 4% (P < 0.01). Sinorphan increased glomerular filtration rate (GFR) and filtration fraction by 10% 1 h after administration and decreased renal plasma flow by 10%. Mean arterial pressure, renal vascular resistance, plasma aldosterone concentration, and renin activity were unmodified. Sinorphan decreased fractional clearance of neutral dextrans over the 34- to 52-A radius range. Applying the changes along with a hydrodynamic isopore with shunt model, sinorphan significantly increased capillary pressure gradient (delta P; 39 +/- 1 vs. 34 +/- 1 mmHg; P < 0.01), whereas ultrafiltration coefficient was unchanged. In conclusion, endopeptidase inhibition increased endogenous plasma ANP and cGMP generation and induced natriuresis through both an increase in filtered load and a decrease in distal tubular reabsorption of sodium. Sinorphan increases GFR, filtration fraction, and delta P, probably through an increase in efferent over afferent arteriolar resistance ratio.