Nitroprusside-Hypotension: Cerebral Blood Flow and Cerebral Oxygen Consumption in Neurosurgical Patients

The effects of nitroprusside-induced hypotension on cerebral blood flow and cerebral oxygen consumption were investigated in nine patients scheduled for cerebral arterial aneurysm surgery. Anesthesia was maintained with nitrous oxide/oxygen and fentanyl; muscle relaxation was achieved with pancuronium; Paco₂ was maintained at 4.79-5.32 kPa. Mean arterial pressure was reduced to 50 mm Hg by nitroprusside infusion after opening of the dura. Measurements were recorded and blood samples were taken 15 min before induction of hypotension, during stable hypotension and 15 min after termination of nitroprusside infusion. Measurements included: cerebral blood flow, using the argon-washin technique, cardiac output (thermodilution), mean arterial pressure and heart rate. Cerebral blood flow averaged 56 ± 6 ml/min. 100 g before hypotension. Nitroprusside produced hypotension but did not significantly alter cerebral blood flow (61 ± 7 ml/min · 100 g). Cerebral blood flow remained virtually at preinfusion values upon cessation of infusion (53 ± 6 ml/min · 100 g). Cerebral oxygen uptake averaged 3 ± 0.2 ml/min · 100 g before hypotension and did not change significantly during hypotension (3.3 ± 0.3 ml/min · 100 g) and after termination of hypotension (2.7 ± 0.3 ml/min · 100 g). In two patients nitroprusside produced a 17 and 20% increase, respectively, in cerebral blood flow with no change in cerebral oxygen consumption, together with a marked increase in cardiac output and heart rate.     

The effect of diuretics on renal hemodynamics during cardiopulmonary bypass

The effect of cardiopulmonary bypass (CPB) on renal hemodynamics was studied in 15 dogs using ¹³³xenon washout. Ten control dogs had no diuretics administered and five diuretic dogs were given furosemide immediately before and during CPB. A catheter was inserted into the right renal artery under fluoroscopic guidance via the left femoral artery and a bolus of ¹³³xenon injected. Washout curves were obtained with a collimater placed over the kidney before CPB and after 15 and 90 min of CPB. Total CPB was undertaken at normothermia using venous gravity drainage, an arterial roller pump, a heat exchanger and a Kolobow membrane oxygenator. Washout curves were analyzed and four components of renal blood flow (RBF) developed: I, cortex; II, juxtamedulla; III, inner medulla; and IV, hilar fat. Percentage of total radioactivity and regional blood flow was derived for each component and total RBF calculated.Total RBF in the control group decreased progressively during CPB (457 → 269 → 158 ml/100 g/min after 90-min CPB). This decrease in RBF was associated with a marked shunt of flow from cortical to juxtamedullary region. Percentage of flow to the cortex decreased as well (68% → 33% → 23% after 90 min) while activity to the juxtamedulla increased (24% → 47% → 50% after 90 min).RBF in the diuretic treated group decreased during CPB but significantly less than in the control group (436 → 397 → 273 ml/100 g/min after 90-min CPB). The intrarenal shunt seen in the control group during CPB was significantly reduced in the diuretic treated group. While percent flow to the cortex was reduced as bypass progressed (67% → 56% → 47% after 90 min), cortical activity remained greater than juxtamedullary (29% → 36% → 38% after 90 min) throughout the 2 hr of bypass. It was apparent from this study that cortical ischemia associated with CPB can be substantially reduced by diuretic therapy during CPB.     

A clinical study of cerebral circulation during extracorporeal circulation

The objective of this study is to clarify the relationship of cerebral blood flow to extracorporeal circulation flow and mean arterial pressure during nonpulsatile extracorporeal circulation under moderate hypothermia. Cerebral blood flow was determined by an argon saturation and desaturation method after that of Pevsner and colleagues with a mass spectrometer in 21 adult patients undergoing cardiac operations. Cerebral blood flow was 25, 33, 35, and 42 ml/100 gm/min, ranging from 19 to 50 ml/100 gm/min, at extracorporeal circulation flow rates of 40, 50, 60, and 70 ml/kg/min, respectively. Cerebral blood flow increased proportionally to extracorporeal circulation flow. Cerebral blood flow scattered almost transversely to mean arterial pressure and was 31 ml/100 gm/min in a hypotensive group (mean arterial pressure 34 to 50 mm Hg) and 34 ml/100 gm/min in another group (mean arterial pressure 51 to 94 mm Hg). Mean arterial pressure did not significantly influence cerebral blood flow. Cerebral oxygen consumption did not remarkably decrease and remained in the reasonable range when cerebral blood flow was 23 to 40 ml/100 gm/min. Subsequently, we assumed that the average cerebral blood flow value of 25 ml/100 gm/min at an extracorporeal circulation flow rate of 40 ml/kg/min also would be in the safe range. All of the patients are living without cerebral complications. We conclude that (1) cerebral blood flow was extracorporeal circulation flow dependent and (2) cerebral blood flow in the safe range was maintained even in the hypotensive range, provided the extracorporeal circulation flow rate was 40 ml/kg/min or higher.     

Effect of indomethacin on renal function in anaesthetized dogs

The inhibitory action of indomethacin administered as a single-dose injection (4 mg/kg) was examined under general anaesthesia in dogs, moderate volume expansion having been induced with physiological saline infusion. At 20 to 30 min after the administration of indomethacin, excretion of Na and water showed a fall of the same extent, GFR remaining stable and the effective plasma flow (C_PAH) declining. RBF estimated by the⁸⁶Rb method decreased from 411±96 ml/min/100 g to 292±±53 ml/min/100 g (p<0.01). This fall was coupled with an intrarenal redistribution of blood flow. While the cortical fraction of renal blood flow increased from 79% to 83.9% (p<0.001), its outer medullary fraction decreased from 17% to 13.2% (p<0.001) and its inner medullary fraction from 4.0% to 2.8% (p<0.05). The renal, primarily the medullary, vasculature is assumed on these grounds to be under the influence of a continuous secretion of prostaglandins which thus seem to be involved in the physiological control of intrarenal distribution of blood flow and of sodium and water excretion.     

Abnormalities in organ blood flow and its distribution during positive end-expiratory pressure.

Current evidence is inconclusive regarding the possibility that positive end-expiratory pressure (PEEP) redistributes flow and may be directly responsible for systemic organ dysfunction. This study tests the hypothesis that PEEP may induce abnormalities in the distribution of cardiac output (CO). Eight anesthetized dogs were studied during (1) 0 cm H2O PEEP (Z1), (2) 15 cm H2O PEEP (P), (3) Z2, and (4) bleeding (B) to reduce the CO to the same level as P. At each of the four periods, a different 15 mu radiolabelled microsphere was injected into the left atrium. Another four dogs were used to varify that each type of microsphere had the same flow distribution. CO fell from 3.1 liters/min to 1.9 during P (P smaller than 0.01) and to 2.0 during B (P smaller than 0.01). Mean arterial pressure (MAP) declined from 102 to 83 mm Hg (P smaller than 0.01) and 86 mm Hg (P smaller than 0.01(, respectively. Left atrial pressure (LAP) rose from 5.0 to 7.9 mm Hg during P (P smaller than 0.01) and fell during B to 2.7 mm Hg. c0 and its distribution were the same during Z1 and Z2. P caused selective reductions in hepatic (52%), adrenal (25%), and bronchial (24%) blood flows (P smaller than 0.01). In contrast, total flow to these organs during B was the same as during Z. Total renal flow was unchanged by P or B, but the cortical:medullary flow ratio increased during P from 24 to 49 (P smaller than 0.01) and was unchanged by B. P induced a decrease in fundal nucosal flow as compared with Z (P smaller than 0.01). Total coronary flow fell from 100 to 64 ml/min during both P and B (P smaller than 0.01). P led to a selective fall in subendocardial flow (67 ml/min X 100 gm) as compared with B (82.5 ML/MIN X 100 gm, P smaller than 0.01) as well as in the subendocardial:subepicardial flow ratio (1.069 vs. 1.112 ml/min X 100 gm, P smaller than 0.05). It is likely that the higher left ventricular filling pressure (LAP) during P as compared with during B compressed the endocardium and induced relative ischemia. Similarly the high airway pressure during P may have impeded bronchial mucosal flow. The causes and consequences of the other P-induced variations in flow are speculative.     

Systemic and renal effects of dopamine in the infant pig

Dopamine is commonly employed in the management of hypotensive patients. Although this medication increases cardiac index (CI) and renal artery (RA) flow in adults, its effect in infants has not been adequately studied. In 13 infant pigs (mean wt 3.05 ± 0.75 kg; age 3–4 weeks) CI, RA flow and systemic blood pressure (BP) were measured at varying renal artery perfusion pressures before and after the administration of dopamine. Pigs were anesthetized with ketamine, intubated, and maintained on a ventilator with succinylcholine. Jugular vein, pulmonary (Swan-Ganz), carotid, and femoral artery catheters were placed. Laparotomy was performed and RA flow was measured with an electromagnetic flow probe. A Blalock clamp was placed around the suprarenal aorta to obtain graded aortic occlusions to pressures of 80 and 50 mm Hg. Dopamine had no significant effect on the CI vs control at 5, 10, 15, 20, 25, or 50 μg/kg/min. BP increased 25 mm Hg on Dopamine (10 μg/kg/min) P > 0.05). RA flow remained stable (318 ± 74 vs 300 ± 68 ml/min) despite reduction in perfusion pressure to 80 mm Hg, suggesting an autoregulatory flow mechanism. At 50 mm Hg perfusion pressure however, RA flow decreased significantly to 220 ± 54 ml/min (P < 0.05) indicating a loss of autoregulation at lower perfusion pressures.Dopamine (10 μg/kg/min) did not change RA flow at control BP (335 ± 76 vs 318 ± 74 ml/min). At 80 mm Hg perfusion pressure however, RA flow fell from 335 ± 74 to 175 ± 50 ml/min (P < 0.001) demonstrating a suppression of renal autoregulation by dopamine. At 50 mm Hg, RA flow was markedly reduced to 22 ± 31 ml/min (P < 0.001). These data suggest: (1) dopamine has no significant effect on CI in infant pigs, (2) an RA flow mechanism is present in infant pigs which protects the kidney at reduced perfusion pressures, and (3) dopamine interferes with autoregulation and may be harmful to the infant kidney in hypotensive states.     

Role of Angiotensin II in Renal Vasoconstriction with Acute Hypoxemia and Hypercapnic Acidosis in Conscious Dogs

To evaluate the role ofrenin-angiotensin in the renal vasoconstriction with combined acute hypoxemia and hypercapnic acidosis preceded by acute hypoxemia, we studied eight conscious mongrel uninephrectomized dogs with chronic renal catheters and controlled sodium intake (80 mEq/24 h ± 4 days). The animals were studied during combined acute hypoxemia and hypercapnic acidosis (Pa_O2 34 ± 1 mm Hg, Pa_CO2 57 ± 1 mm Hg, pH 7.20 ± 0.01) preceded by 80 min of acute hypoxemia (Pa_O234 ± 1 mm Hg) during: (a) intrarenal infusion of vehicle (n = 8); or (b) intrarenal administration of the angiotensin II antagonist [Sar¹, Ala⁸]-AII, 70 ng kg^?1 min^?1 (n = 8). The combination of acute hypoxemia and hypercapnic acidosis resulted in diminished effective renal plasma flow and increased renal vascular resistance during intrarenal vehicle infusion. Intrarenal [Sar¹, Ala⁸]-AII did not abolish the renal vasoconstriction in the initial 20 min of this combined blood gas derangement but resulted in a more prompt return of the renal vascular variables toward control levels with continuation of the blood gas derangement for an additional 20 min, suggesting a role for angiotensin in renal vasoconstriction. These observations suggest that while rennin—angiotensin may not mediate the initial renal vasoconstriction in the first 20 min of combined acute hypoxemia and hypercapnic acidosis, in uninephrectomized conscious dogs, it attenuates the spontaneous recovery of renal hemodynamic variables to baseline as the blood gas derangement continues.     

Effects of fenoldopam on renal blood flow and systemic hemodynamics during isoflurane anesthesia.

The authors compared the systemic hemodynamic and renal vascular effects of hypotension induced by fenoldopam with those produced by the most commonly used hypotensive agent, sodium nitroprusside, in 10 dogs. Mean arterial pressure decreased 26% +/- 3% from control following infusion with fenoldopam, and 30% +/- 2% following infusion with sodium nitroprusside (these decreases were not significantly different between the groups). Renal blood flow (RBF) was preserved during fenoldopam-induced hypotension (214 +/- 16 mL/min at baseline and 197 +/- 16 mL/min after fenoldopam-induced hypotension). In contrast, RBF decreased from 223 +/- 17 mL/min to 167 +/- 12 mL/min during sodium nitroprusside-induced hypotension (P less than 0.02). The differences in RBF between the two groups occurred in spite of the fact that cardiac output and pulmonary capillary wedge pressure were kept similar between the two groups. The authors conclude that fenoldopam, a selective dopamine1 (DA1) receptor agonist, preserves blood flow to the kidney during induced hypotension. On the other hand, sodium nitroprusside is a nonselective arteriolar and venous vasodilator that redistributes blood flow away from the kidneys during induced hypotension.     

The influence of the cyclosporine vehicle, cremophor EL, on renal microvascular blood flow in the rat.

Cyclosporine nephrotoxicity may be due to glomerular hypoperfusion. Previous experimental and clinical studies have demonstrated a decrease in renal blood flow and an increase in renal vascular resistance. Cremophor EL, which is the vehicle in which CsA is dissolved, is thought to be a factor involved in intrarenal arteriolar vasoconstriction. To determine the relative contributions of the vehicle and CsA to intrarenal arteriolar vasoconstriction, we used in vivo videomicroscopy and Doppler velocimetry to measure changes in renal microvascular blood flow in the rat. A 5-min intravenous infusion of 20 mg/kg of CsA resulted in a 17% mean reduction (P less than 0.05) in the diameter of preglomerular interlobular arterioles and an associated 60% reduction (P less than 0.05) in microvascular blood flow by 15 min. Cremophor EL/ethanol equivalent caused less vasoconstriction (up to 10%) but resulted in a 42% mean decrease (P less than 0.05) in microvascular blood flow, probably secondary to a 38% mean decrease (P less than 0.05) in cardiac output and 13% decrease in arterial pressure. We conclude that cremophor EL does contribute to in vivo reduction of preglomerular microvascular blood flow in the rat. This may be particularly important when using this intravenous preparation in the study of CsA nephrotoxicity.     

The effects of etomidate on cerebral metabolism and blood flow in a canine model for hypoperfusion

The effects of etomidate, a nonbarbiturate cerebral metabolic depressant, on cerebral metabolism and blood flow were studied in 29 dogs during cerebral hypoperfusion. Three groups of animals were studied during a 45-minute normotensive and a 30-minute hypotensive period: 10 control animals without etomidate, 11 animals receiving a 0.1-mg/kg etomidate bolus followed by an infusion of 0.05 mg/kg/min etomidate (low-dose group), and eight animals receiving doses of etomidate sufficient to suppress electroencephalographic bursts (high-dose group). The mean arterial pressure fell to similar levels (p less than 0.05) during hypotension in all three groups (40 +/- 5, 38 +/- 3, and 27 +/- 6 mm Hg, respectively). The mean cerebral oxygen extraction fraction rose (p less than 0.05) from 0.23 +/- 0.02 to 0.55 +/- 0.08 in the five control animals tested and from 0.33 +/- 0.02 to 0.53 +/- 0.02 in the seven animals tested in the low-dose group, but did not increase (p greater than 0.05) in the four animals tested in the high-dose group (0.24 +/- 0.03 to 0.23 +/- 0.05). Mean cerebral blood flow levels decreased in all groups during hypotension (p less than 0.05): 42 +/- 3 to 21 +/- 4 ml/100 gm/min (52% +/- 12% decrease) in the five animals tested in the control group, 60 +/- 8 to 24 +/- 6 ml/100 gm/min (56% +/- 13% decrease) in the four animals tested in the low-dose group, and 55 +/- 8 to 22 +/- 3 ml/100 gm/min (60% +/- 4% decrease) in the four animals tested in the high-dose group. In summary, the cerebral oxygen extraction fraction increased in the control animals and low-dose recipients during hypotension, suggesting the presence of threatened cerebral tissue. In contrast, the cerebral oxygen extraction did not change during hypotension when high-dose etomidate was administered. It is concluded that high-dose etomidate may preserve the cerebral metabolic state during hypotension in the present model.     

Renal effects of glucagon in dogs with hemorrhagic hypotension

Previous studies in dogs with hemorrhagic hypotension, where the arterial blood pressure was maintained constant at 65 to 70 mm Hg, demonstrated that the intravenous infusion of glucagon at 5 μg/min may cause marked increments in the glomerular filtration rate and renal blood flow. To investigate the mechanism of this response we studied a similar model with micropuncture techniques. In 10 dogs, an acute hemorrhage raised intrarenal vascular resistance by 60%. By use of the Gomez equations (Gomez, D. M. Evaluation of renal resistances with special reference to changes in essential hypertension. J. Clin. Invest.30: 1143, 1951.), it was demonstrated that the infusion of glucagon produced predominant preglomerular vasodilatation, though there was efferent dilatation as well. Glomerular permeability was not changed by the glucagon infusion. An increase in cardiac output or redistribution of glomerular flow did not contribute to the renal effects of glucagon in this model. Glucagon is able to raise glomerular filtration rate in dogs with hemorrhagic hypotension through its ability to dilate predominantly the afferent arteriole.     

Renal function and intrarenal hemodynamics in acutely hypoxic and hypercapnic rats

On the basis of microsphere distribution, inert gas washout, and standard clearance data, the effects of acute hypoxia and hypercapnia on the kidney were studied in anesthetized, mechanically ventilated rats. Moderate hypoxia (mean PO2, 48 mm Hg) did not significantly change diuresis, GFR, and tubular sodium rejection. Due to a decrease in renal vascular resistance (R) from 40.1 to 31.8 mm Hg ml-1 min, mean renal blood flow stayed constant in spite of a significant drop in mean arterial blood pressure. Hypoxic changes in R were not accompanied by significant changes in intrarenal distribution of blood flow (IDBF). In severe hypoxia (PO2 less than 45 mm Hg) with oliguria and marked arterial hypotension, R was the lowest of all groups (28.8 mm Hg ml-1 min). Hypercapnia did not significantly change the renal excretory parameters, although an increase in R (without change in IDBF), together with a decrease in MAP caused a marked drop in mean renal blood flow. From these studies we conclude: 1) in the anestheized rat, acute hypoxia caused significant changes in intrarenal hemodynamics without changes in excretory function, 2) hypoxic renal vasodilation persists even in severe hypotension with oliguria and anuria, 3) in acute hypoxia and hypercapnia, changes in renal blood flow and renal vascular resistance are not accompanied by significant changes in IDBF.     

Cardiovascular function during controlled hypotension induced by adenosine triphosphate or sodium nitroprusside in the anesthetized dog

The present study was undertaken to compare the hemodynamic effects of adenosine triphosphate (ATP) and sodium nitroprusside (NP) given in equieffective doses to induce hypotension during halothane anesthesia. Eight dogs, instrumented with pressure and ultrasonic dimension transducers for assessment of left ventricular (LV) performance, were given both NP and ATP. Regional blood flow was measured by radioactive microspheres. After 20 min of infusion, both drugs decreased systemic arterial pressure by 36% with minimal changes in cardiac index (CI), LV end-diastolic pressure, or heart rate. However, hypotension produced by ATP was associated with a greater CI (3.84 +/- 0.32 vs 2.97 +/- 0.35 L X min-1 X m-2) than was NP and also associated with a further decrease in systemic vascular resistance (14.4 +/- 1.4 vs 17.7 +/- 2.2 mm Hg X L-1 X min X m2). Left ventricular global function, measured by the slope of the linear regression line of the LV end-systolic pressure-diameter relation (Ees), did not change significantly after either drug. Blood flow to the coronary bed was significantly greater with ATP than with NP (231.6 +/- 30.6 vs 81.7 +/- 6.1 ml X min-1 X 100 g-1). Except for an increase in hepatic arterial blood flow with NP, neither ATP nor NP significantly altered blood flow to the brain, spinal cord, spleen, kidney, jejunum, muscle, and skin. Controlled hypotension by ATP was stable and rapidly reversible without rebound hypertension. The results of this study indicate that ATP is a rapidly acting, effective hypotensive agent that compares favorably with NP.     

Subarachnoid blockade alters homeostasis by modifying compensatory splanchnic responses to hemorrhagic hypotension

To demonstrate that sympathetic responses transmitted by the splanchnic nerve help maintain intravascular stability, 12 mongrel dogs (35-45 kg each), anesthetized with pentobarbital, were given two separate but identical hypotensive stimuli (mean arterial blood pressure of 60 mm Hg for 15 min) by the withdrawal of appropriate amounts of blood. The first stimulus was performed in the absence of drug or surgical manipulation. The second stimulus was performed after animals were subjected to no intervention (n = 4), bilateral splanchnic nerve section (n = 4), or spinal anesthesia (n = 4). Before and 10 min after the onset of hypotension, arterial epinephrine concentration and adrenal medullary and abdominal organ blood flow were measured. In the group without intervention, the second hypotensive stimulus (like the first) elicited 3-fold increases in adrenal medullary blood flow, 40-fold increases in arterial epinephrine concentration, and a 61% reduction in abdominal organ blood flow (P greater than 0.002). The volume of blood withdrawn to produce hypotension was similar (approximately 21 ml.kg-1). Bilateral splanchnic nerve section attenuated the adrenal medullary blood flow, arterial epinephrine concentration, and abdominal organ blood flow responses to hypotension by 86, 64, and 66%, respectively (P less than 0.008), and the blood volume withdrawn was reduced by 42% (P less than 0.02). Spinal anesthesia eliminated the adrenal medullary blood flow response to hypotension, attenuated the arterial epinephrine concentration and abdominal organ blood flow responses by 78 and 57%, respectively (P less than 0.01), and decreased the blood volume extracted by 55% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in cerebral CO2 responsivity over time during isoflurane anesthesia in the dog

We assessed cerebrovascular responsivity to changes in arterial carbon dioxide tension (PaCO2) during 3 h of 1 MAC isoflurane anesthesia to determine whether it parallels previously reported time-dependent decrease in normocapnic cerebral blood flow (CBF). Twelve dogs were studied under pentobarbital anesthesia (30 mg kg iv bolus) and twelve dogs under isoflurane anesthesia (1.4% end-tidal). In six animals of each anesthetic group, hypocapnia was compared to normocapnia; in the remaining six animals, hypercapnia was compared to normocapnia. At 1, 2, and 3 h after anesthesia induction, and again 10 min after blood gas alteration (hypocapnia or hypercapnia) normocapnic CBF was determined by the radiolabelled microsphere method. In animals receiving pentobarbital, total CBF during normocapnia, hypocapnia, and hypercapnia at 1 h was 40 +/- 4, 24 +/- 3, and 113 +/- 13 ml min 100g, respectively, and there was no significant change (p >0.05) at each respective level of CO2 over the 3 h of the study. Cerebral metabolic rate for oxygen (CMRO2) was unchanged with time or CO2 alteration. CO2 responsivity (change in CBF/change in PaCO2) during hypercapnia was 0.8 +/- 0.2 ml min 100g mm Hg and during hypercapnia was 3.4 +/- 0.6 ml min 100g mm Hg at 1 h and both were unchanged from those value at 3 h. In animals receiving isoflurane and subjected to hypocapnia, total CBF during normocapnia at 1 h was 97 +/- 10 ml min 100 g and declined to 56 +/- 9 ml min 100 g at 3 hr (p <0.05). Over the same time period (1-3 h), hypocapnic CBF decreased from 44 + 5 to 27 +/- 3 ml min 100g (p <0.05). In animals receiving isoflurane and subjected to hypercapnia, normocapnic CBF decreased from 68 +/- 10 to 46 +/- 6 ml min 100 g at 3 h (p <0.05) and hypercapnic flow over the same time declined from 184 +/- 24 ml min 100 g to 135 +/- 18 ml min 100g (p <0.05). CMRO2 was not changed by either time or CO2 alteration. Between 1 and 3 h, CO2 responsivity during hypecapnia decreased from 4.1 +/- 0.9 to 1.8 +/- 0.4 ml min 100 g mm Hg (p <0.05). CO2 responsivity during hypocapnia decreased from over the same period decreased from 9.0 +/- 1.0 to 5.1 +/- 0.9 ml min 100 g mm Hg (p <0.05). Similar time-dependent trends were observed in most brain regions. We conclude that normocapnic CBF and cerebral CO2 responsivity decrease over time during isoflurane anesthesia and that these changes are not caused by changes in brain metabolism.     

Cardiovascular function during induced hypotension by fenoldopam or sodium nitroprusside in anesthetized dogs.

Fenoldopam, a selective dopamine1 receptor agonist, has been recommended for induced hypotension because it effectively lowers arterial blood pressure and improves renal perfusion. We examined cardiovascular functions during hypotension induced by fenoldopam or sodium nitroprusside. In eight halothane-anesthetized dogs, the left ventricle (LV) was instrumented with pressure and ultrasonic dimension transducers for the assessment of LV contractility using the analysis of the pressure-diameter relationship. Blood flow distribution was measured by radioactive microspheres. Doses of fenoldopam and nitroprusside were titrated to reduce mean arterial blood pressure to 60 mm Hg. After 40 min of hypotension, fenoldopam and nitroprusside caused similar increases in heart rate (17% +/- 4% vs 19% +/- 10%, respectively) and decreases in systemic vascular resistance (-24% +/- 5% vs -27% +/- 4%). Hypotension induced by fenoldopam was associated with higher LV end-diastolic pressure (4.4 +/- 0.6 vs 2.5 +/- 1.1 mm Hg) and end-systolic meridional wall stress (33.0 +/- 4.3 vs 17.8 +/- 2.1 g/cm2) when compared with nitroprusside. There were no significant changes in cardiac output and cardiac contractility as expressed by the slope (Ees) of the LV end-systolic pressure-diameter relationship, velocity of shortening of the diameter, and percentage of wall thickening of the LV. In contrast to nitroprusside, which decreased renal blood flow from 197 +/- 19 to 163 +/- 15 mL/min, renal blood flow increased during fenoldopam-induced hypotension from 187 +/- 20 to 239 +/- 18 mL/min. The increase in renal perfusion was similar in upper, middle, and lower regions of the kidney; however, it was more in the medulla compared with the cortex (37% +/- 17% vs 25% +/- 7%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute effect of passive Heymann nephritis on renal blood flow and glomerular filtration rate in the rat: role of the anaphylatoxin C5a and the alpha-adrenergic nervous system.

In earlier studies, we have shown that induction of passive Heymann nephritis (PHN) by intrarenal infusion of anti-Fx1A antibodies provokes an immediate fall in renal blood flow (RBF) and glomerular filtration rate (GFR). This was probably mediated via the complement system, as infusion of the F(ab')2 fraction of anti-Fx1A did not reduce RBF and GFR. In the present study, the effects of alpha-adrenergic blockade upon the acute hemodynamic changes during induction of PHN and of C5a infusion were studied. Group 1 was infused with anti-Fx1A antibodies during blockade of the sympathetic nervous system with the alpha-blocker phentolamine; control animals were treated similarly, but infused with normal rat IgG. Group 2 was infused with the anaphylatoxin C5a, normally produced during complement activation, and compared with control animals infused with saline. In group 1, RBF did not differ from control animals after the infusion of anti-Fx1A antibodies (6.6 +/- 0.5 compared to 7.3 +/- 1.0 ml/min/g in the controls). GFR in the left, antibody-infused kidney fell compared to controls, and was 0.25 +/- 0.08 ml/min/g at the end of the experiment compared to 0.60 +/- 0.13 ml/min/g (p less than 0.05 with Student's t test, p = 0.07 with two-way analysis of variance (ANOVA). GFR in the right kidney remained unchanged compared to controls. In group 2, C5a induced a significant fall in RBF (from 7.9 +/- 0.9 to 3.1 +/- 0.4 ml/min/g kidney weight), significantly different from control animals where it fell from 8.1 +/- 0.5 to 6.8 +/- 0.7 ml/min/g (p less than 0.0001 with two-way ANOVA, p less than 0.001 with t test).(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic measurements during controlled hypotension by nitroglycerin (author's transl)

In nine patients undergoing neurosurgical operation for cerebral aneuryms haemodynamic measurements were made before, during and after continuous intravenous administration of Nitroglycerin at a mean dose of 6.5 micrograms/kg . min. Within 15 min of the start of the infusion mean arterial pressure fell from 94.2 +/- 10.5 to 73.4 +/- 11.1 mm Hg. A further decrease of mean arterial pressure even by a substantial raising of the Nitroglycerin dose was not possible. 15 min after the discontinuation of Nitroglycerin administration mean arterial pressure rose to the preinfusion level. The decrease of stroke volume index from 40.8 +/- 9.9 to 31.0 +/- 7.3 ml/m2 was partially compensated by an increase of heart rate from 65.9 +/- 9.6 to 77.7 +/- 19.4 beats/min. Consequently cardiac index fell only slightly from 2.9 +/- 0.6 to 2.5 +/- 0.5 ml/min . m2. The right atrial pressure decreased to 3.3 +/- 2.9 mm Hg, the mean pulmonary arterial pressure to 6.3 +/- 1.9 mm Hg and the pulmonary capillary wedge pressure to 2.3 +/- 2.1 mm Hg. The significant fall of total peripheral resistance to 983 +/- 194 dyn x s/cm5 (p less than 0.05) and the decrease of left ventricular stroke work index to 34.7 +/- 11.5 g . m/m2 contributed to reduce myocardial oxygen consumption. The authors conclude that, because of its effect on blood pressure, it reversibility of action and its absence of adverse side effects Nitroglycerin is a valuable agent for controlled hypotension.     

Intrarenal blood flow in carotid sinus nerve stimulation and hemorrhage in dogs.

The present study was undertaken to compare the role of the sympathetic nervous system, in hemorrhage, with that of hypotension in producing renal blood flow (RBF) redistribution. Ten mongrel dogs were prepared for the determination of RBF distrubition by injecting 85Kr dissolved in saline into the renal artery to obtain renal radioactivity curves. RBF distribution was determined a) at control, b) during a 15-min period of hypotension produced by electrical stimulation (10 v-60Hz) of the left carotid sinus nerve (nerve of Hering), c) 15 min after hemorrhage to a blood pressure equivalent to that of stimulation and d) during hemorrhage plus a 15-min period of stimulation. Hypotension caused by stimulation left component I blood flow unchanged (at approximately 492 ml/min/100 g) but resulted in an increase in component II flow from 93 +/- 8 to 155 +/- 20 ml/min/100 g. Hemorrhage caused a 60% reduction in component I blood flow rate, leaving component II unchanged. Partial reversal of hemorrhage effects on distrubiton of RBF was obtained by restimulation of the nerve of Hering. It appears that RBF distribution, as controlled by the carotid sinus, may involve primarily component I flow, with the redistribution between components I and II during hemorrhage possibly involving other mechanisms.     

Prevention of acute cyclosporin nephrotoxicity by verapamil and atrial natriuretic factor in the rat

Nephrotexicity is the most common and important side-effectof cyclosporin (CsA) therapy. CsA alters renal haemodynamicswith a reduction in renal blood flow (RBF) and glomerular filtrationrate (GFR) and a significant increase in renal vascular resistances(RVR). The present experimental study investigates whether verapamilor atrial natriuretic factor (ANF) are able to prevent the nephrotoxicityof CsA. All studies were conducted in an in-situ autoperfused rat kidneymodel which allows continuous measurement of renal blood flowwithout dissection of the renal artery. CsA as a 40 mg/kg bolus dose significantly decreased RBF (from2.15±0.1 and 2.19±0.1 before CsA, to 1.29±0.16ml/min/100 g BW, 60 mm after CsA administration) (P<0.05),and GFR (from 0.14±0.1 and 0.13±0.01 before CsA,to 0.08±0.01 ml/min/100 g BW, 60 min after CsA administration)(P<0.05). CsA significantly increased RVR (from 9.5±0.73and 9.8±0.78 before CsA, to 16.7±2.9 mmHgxmin/ml60 min after CsA administration) (P<0.05). Verapamil pretreatment(as continuous intrarenal infusion at the rate of 1.25 µg/kg/min)attenuated the fall in GFR (from 0.16±0.01 and 0.19±0.03ml/min/100 g before CsA to 0.20±0.05 ml/min/100 g BW,60 mm after CsA administration) (NS) and in RBF (from 2.42±0.2and 2.6±0.22 ml/min/100 g before CsA to 1.79±0.17ml/min/100 g BW, 60 min after CsA administration (P<0.05).Pretreatment with ANF (as continuous intrarenal infusion atthe rate of 2.5 µg/kg/min) protected GFR (from 0.11±0.02and 0.18±0.03 ml/min/100 g before CsA, to 0.11±0.03ml/min/100 g BW, 60 min after CsA administration) (NS) and RVR(from 9.53±0.6 and 8.95±0.74 mmHgxmin/ml beforeCsA to 11.93±1.19 minHgxmin/ml, 60 min after CsA administration)(NS)and attenuated the fall in RBF (from 2.17±0.11 and 2.2±0.14ml/min/100g before CsA to 1.56±0.25 ml/min/100 g BW 60mm after CsA administiation)(P<0.05) when compared with initialvalues. These studies suggest that verapamil and ANF can prevent CsA-inducedrenal toxicity. Further studies should evaluate their usefulnessin clinical practice.