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The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs

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Summary

The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n=5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n=6, posttreatment) an intra-aortic injection of diltizem (5 µg·min−1·kg−1) beginning at the end of ischemia until the 7th day. Group C (n=7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149±16 (preischemic) to 129±29 ml·min−1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29±15% (group B,P 0.05) and 14±13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group. In group C, the glomerular filtration rate was significantly less reduced than in group A (34±1.8 preischemically to 17±5.4 on day 1,P 0.05 and 20±4.1 ml·min−1 on day 7,P 0.05). Plasma renin activity increased in both diltiazem groups, more pronounced so in group B (from 3.7±1.0 on day 1 to 16.2±7.9 ng ATI·ml−1·h−1 on day 7,P 0.05). In contrast to groups A and B, the increase in fractional sodium excretion was less pronounced in group C. Likewise, the decrease in free water-reabsorption was less marked than in groups A or B. It was apparent that diltiazem, when administered pre- and post-ischemically, preserved glomerular filtration rate and renal blood flow. When diltizem was given solely postischemically there was an improvement in renal blood flow, but no significant influence on glomerular filtration rate. We therefore conclude that mainly tubular factors, in addition to the attenuation of postischemic vasoconstriction, are involved in the protective effect of diltiazem on postischemic acute renal failure in conscious dogs.

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Abbreviations

ARF:

acute renal failure

Cosmol :

clearance of osmolarity

ENa :

urinary excretion rate of sodium

FENa :

fractional excretion rate of sodium

GFR:

glomerular filtration rate

HR:

heart rate

NE:

norepinephrine

PAM:

mean arterial blood pressure

PRA:

plasma renin activity

RBF:

renal blood flow

RVR:

renal vascular resistance

TH2O :

free water reabsorption

VU :

urine volume

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Wagner, K., Schultze, G., Molzahn, M. et al. The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs. Klin Wochenschr 64, 135–140 (1986). https://doi.org/10.1007/BF01732639

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Key words

  • Acute renal failure
  • Calcium antagonists
  • Conscious dogs
  • Glomerular filtration rate
  • Renal blood flow