Effects of Hemorrhage on Regional Blood Flow Distribution in Dogs and Primates

109

A B S T R A C T The effects of hypotensive hemorrhage (HH) on renal hemodynamics and plasma renin activity (PRA) during prostaglandin (PG) synthesis inhibition were examined in three groups ofdogs. In each group of animals arterial blood pressure was lowered by a 30% decrement. In the first group of eight control animals, HH was not associated with a significant change in glomerular filtration rate (GFR, 42-36 ml/min, NS); renal blood flow (RBF) declined significantly, from 234 to 171 ml/min, P < 0.05. In the second group of eight animals, pretreated with RO 20-5720 (RO, 2 mg/kg), a competitive inhibitor of PG synthesis, HH was associated with a significant fall in GFR (43-17 ml/min, P < 0.001) and RBF (195-89 ml/min, P < 0.001). In the third group of eight animals, pretreatment with indomethacin (IN, 10 mg/kg), a chemically dissimilar PG inhibitor, HH was also associated with a significant fall in GFR (38-8 ml/min, P < 0.001) and RBF (150-30 ml/min, P < 0.001). Renal denervation attenuated this renal ischemic effect of HH in the presence of PG inhibition. In the RO group, GFR (34 vs. 17 ml/min, P < 0.005) and RBF (145 vs. 89 ml/min, P < 0.025) were significantly greater in denervated vs. innervated kidneys during HH. Similarly, in animals treated with IN, a significantly higher GFR (28 vs. 8 ml/min, P < 0.005) and RBF (101 vs. 30 ml/min, P < 0.005) occurred in denervated as compared to innervated kid- neys during HH. With HH, the increase in PRA in the control group (3.34-11.68 ng/ml per h, P < 0.005) was no different than that observed in the RO group (4.96-18.9 ng/ml per h, P < 0.001) or IN group (4.71-17.8 ng/ml per h, P < 0.001). In summary, the present results indicate that renal PG significantly attenuate the effect of HH to decrease GFR and RBF. Furthermore, renal denervation exerts a protective effect against the enhanced renal ischemic effects which occur in the presence of PG inhibition during HH. Finally, PG inhibition does not alter the effect of HH to cause anl increase in PRA.

Section: Resultsmentioning

confidence: 73%

The Role of Renal Nerves and Prostaglandins in Control of Renal Hemodynamics and Plasma Renin Activity during Hypotensive Hemorrhage in the Dog

Henrich¹,

Anderson²,

Berns³

et al. 1978

109

“…In contrast, no significant reduction in renal blood flow occurred. We have previously reported that during hemorrhagic hypotension to 72 mm Hg in pregnant rabbits, renal blood flow was 16±3.2% of CO (5), and renal vasodilatation (12) and preservation of renal blood flow during hemorrhagic hypotension have been reported in dogs and primates (13). These studies would indicate that uterine blood flow is not maintained as well as renal blood flow with severe hypotension induced by ganglionic blockade.…”

Section: Discussionmentioning

confidence: 92%

The effect of changes in perfusion pressure on uteroplacental blood flow in the pregnant rabbit.

Venuto¹,

Cox²,

Stein³

et al. 1976

A B S T R A C T The effect of perfusion pressure on uteroplacental blood flow was determined in pregnant rabbits utilizing the radioactive microsphere method.Control mean arterial pressure, 93 mm Hg±2.6 SEM, was raised by carotid ligation to 109±4.1 mm Hg and then reduced with antihypertensive drugs to 74+1.3 mm Hg. Over this range of pressure there was no significant change in cardiac output, 605+36, 523+37, and 540±39 ml/min; or uteroplacental blood flow, 30+3.2, 27±5.2, and 29±4.5 ml/min, respectively. When prostaglandin synthesis was inhibited with either indomethacin or meclofenamate (2 mg/kg), uterine vascular resistance was higher but maintenance of uteroplacental flow occurred over a perfusion pressure of 89±6.7-115 +9.3 mm Hg. With more severe hypotension induced with trimethaphan, control arterial pressure fell from 92±2.4 to 39+0.9 mm Hg, cardiac output fell from 514 +17 to 407+22 ml/min (P < 0.025) and uteroplacental blood flow fell from 6.1±0.9 to 2.5±0.9% of cardiac output (P<0.05), which represented an absolute fall from 32.4±5 to 10.6±3 ml/min (P <0.025). There was no significant change in renal blood flow expressed as percentage of cardiac output, 14.9+2 and 13±1.5%, or in absolute flow, 75+77 and 54+7 ml/min with trimethaphan-induced hypotension.These studies indicate that uteroplacental blood flow is maintained relatively constant over a range of perfusion pressure of 60-140 mm Hg in both normal and prostaglandin-inhibited pregnant rabbits. However, with reduction in pressure to 36-42 mm Hg, uteroplacental blood flow falls, expressed as a percentage of cardiac output and in absolute flow.

“…The protection afforded by the prophylactic administration of furosemide in several models of ischemic acute tubular necrosis has never been clearly explained (35) but evokes an intriguing parallel to the prevention of mTAL anoxic damage during isolated perfusion by decreasing 02 demand by cells. Indeed, the redistribution of cortical flow in favor ofthe medulla, an early event in hypotension (36), and the profound disproportionate fall in GFR in acute renal failure might be viewed, at least in part, as a regulatory mechanism developed to protect the mTAL from the dangerous and precarious equilibrium between 02 demand and supply within the outer medulla of the kidney.…”

Section: Discussionmentioning

confidence: 99%

Selective vulnerability of the medullary thick ascending limb to anoxia in the isolated perfused rat kidney.

Brezis¹,

Rosen²,

Silva³

et al. 1984

230

106

As bstract. A specific anatomical lesion sharply localized to the cells of the medullary thick ascending limbs (mTAL) and characterized by mitochondrial swelling progressing to nuclear pyknosis and cell death is elicited reproducibly in isolated rat kidneys perfused for 15 or 90 min with cell-free albumin-Ringer's medium gassed with 5% Co2, 95% 02 (02 content, 1.5 vol/100 ml). The lesion, involving about half of mTALs, appears first in mTALs removed from vascular bundles and near the inner medulla, areas most likely to be anoxic. Hypoxic perfusion (02 content 0.12 vol/100 ml) exaggerates the lesion, wiping out gradations of damage and extending it to all mTALs. 02-enriched perfusions using rat erythrocytes (02 content 7.1 vol/100 ml) completely eliminates the lesion (unless gassed with carbon monoxide). Simi Oxypherol, Alpha-Therapeutic, Los Angeles, CA) was used as a blood substitute instead of the regular perfusion medium. Monitoring of oxygenationIn all experimental groups, the Po2 ofthe perfusate was monitored using a blood gas monitor (PHM 73, Radiometer, Copenhagen). In groups A Po2 (mmHg) Figure 1. Expected oxygen dissociation curves for blood (hematocrit 45 and 14%), hemoglobin, FC-43 emulsion, and albumin. The points represent actual measurements during perfusions with erythrocytes (0), hemoglobin 3-4 g/100 ml (X) or 4-5 g/100 ml (0), FC-43 emulsion (A), and albumin (-).and B, the 02 content was calculated using the constant of solubility of 02 in plasma, and confirmed by direct measurement in 10 randomly selected samples. In group C the 02 content was measured directly by volumetry using a Lex 02 con (Lexington Instrument Corp., Waltham, MA). As shown in Fig. 1 The histological evaluation was completed by one of us in a "blinded" fashion; that is, without knowledge of experimental conditions. Three zones of the inner stripe were analyzed: upper third: all mTALs intersecting a line immediately adjacent to outer stripe (within -0.2 mm); middle third: all mTALs intersecting a line drawn midway between the borders of the inner stripe; and lower third: all mTALs intersecting a line immediately adjacent to the inner medulla (within -0.2 mm).These points were chosen for analysis because they provided areas in which topographical landmarks were easily ascertained. A percentage score was used to indicate the fraction oftubules involved with minimal to mild (chromatin margination, minor degrees of mitochondrial swelling), moderate (blatant mitochondrial swelling with limited nuclear pyknosis), or severe (blatant mitochondrial swelling with extensive nuclear pyknosis and cell fragmentation) changes. Between 68 and 272 tubules (mean 137) were evaluated per kidney in a total of 61 kidneys.The data are presented as mean±SEM. Statistical analysis was by the t test, unless specified otherwise.