Adrenergic regulation of blood pressure in chronic renal failure.

Previous investigations have suggested that significant hypotension during hemodialysis may result from abnormalities of sympathetic nervous system activity. To further evaluate these phenomena, plasma dopamine beta-hydroxylase (D beta H) and cold pressor test (proposed indexes of efferent sympathetic nervous system activity) and amyl nitrite inhalation (an index of the entire baroreceptor reflex arc) were studied in two groups of patients: group I, patients exhibiting a mean arterial pressure decrease to less than 70 mm Hg during less than 10% of dialyses; group II (hemodialysis hypotension), patients with a mean arterial pressure decrease to less than 70 mm Hg during more than 90% of dialyses. The groups were similar with respect to plasma renin activity, renin response to ultrafiltration, age, duration of dialysis, nerve conduction velocity, plasma protein concentration, hematocrit, dialysis weight change, resting heart rate, sex, race, blood pressure and heart rate response to cold pressor test, and 125I-albumin plasma volume. Supine mean arterial pressure was higher in patients with hemodialysis hypotension than in patients without hemodialysis hypotension (group I) both before and after dialysis. Plasma D beta H activity was significantly higher in patients with hemodialysis hypotension (group II) than in group I both before and after dialysis. Amyl nitrite inhalation, expressed as change in delta R-R interval/mean arterial pressure decrease, was less in hemodialysis hypotension patients. These results suggest that hemodialysis hypotension may result from a lesion in the baroreceptors, cardiopulmonary receptors, or visceral afferent nerves. Furthermore, elevated mean arterial pressure in patients with hemodialysis hypotension may be neurogenic in origin, as reflected by plasma D beta H activity, and appears similar to the hypertension that follows baroreceptor deafferentation of experimental animals.     

Alterations in the Baroreceptor Reflex in Conscious Dogs with Heart Failure

The effectiveness of the baroreceptor reflex in conscious dogs with experimental cardiac hypertrophy and heart failure was compared with that in a group of normal conscious dogs. Cardiac hypertrophy and heart failure were produced by tricuspid avulsion and progressive pulmonary stenosis. The sensitivity of the baroreceptor reflex to transient hypertension was assessed by determining the slope of the regression line relating the prolongation of the R-R interval to the rise in systolic arterial pressure during the transient elevation of arterial pressure induced by an intravenous injection of 1-phenylephrine. The mean slope averaged 22.4+/-2.3 msec/nm Hg in 16 normal animals. 23.1 +/-1.5 in five sham-operated animals, and was significantly reduced to 8.3 +/-0.8 in 10 dogs with hypertrophy alone (P < 0.001), and to 3.3+/-0.5 in nine dogs with heart failure (P < 0.001). The response to baroreceptor hypotension was compared during bilateral carotid artery occlusion (BCO) in six normal and six heart failure dogs previously instrumented with Doppler flow transducers on the superior mesenteric and renal arteries. During BCO, in normal dogs arterial pressure increased 52+/-4 mm Hg, heart rate 33+/-2 beats/min, mesenteric resistance 0.17+/-0.03 mm Hg/ml per min, and renal resistance 0.37+/-0.10 mm Hg/ml per min. In the heart failure group all of these variables increased significantly less (P < 0.01); arterial pressure rose 25 +/-3 mm Hg, heart rate 13 +/-4 beats/min, mesenteric resistance 0.04+/-0.007 mm Hg/ml per min, and renal resistance 0.18+/-0.09 mm Hg/ml per min.Thus, in heart failure, all measured systemic and regional circulatory adjustments consequent to baroreceptor hypo- and hypertension are markedly attenuated. This study demonstrates a profound derangement of a major cardiovascular control mechanism in experimental heart failure.     

Diversity in supercoupling of beta 2-adrenergic receptors in orthostatic hypotension

Orthostatic hypotension is a clinical condition that frequently involves abnormal adrenergic control of cardiovascular function. Adrenergic function was studied in six patients with symptomatic orthostatic hypotension and in 11 age-matched healthy subjects. The patients demonstrated higher supine mean arterial pressures (MAP; 103 +/- 8 versus 86 +/- 4 mm Hg) and orthostatic hypotension (delta MAP -70 +/- 5 versus +15 +/- 2 mm Hg, p less than 0.001) compared with normal subjects. The delta MAP in phase II of the Valsalva maneuver was significantly greater (-31 +/- 4 versus -7 +/- 4 mm Hg, p less than 0.002) and phase IV heart rate response was blunted (-5 +/- 3 versus -30 +/- 8 beats/min, p less than 0.02) in these patients. More isoproterenol was required to increase heart rate by 25 beats per minute in patients with hypotension (810 +/- 670 versus 3.1 +/- 1.3 micrograms, p less than 0.05), indicating marked chronotropic hyposensitivity. Leukocyte beta 2-adrenergic receptor densities were similar in patients and controls. beta 2-Adrenergic receptor coupling, however, was elevated in patients with hypotension when compared with control subjects (ratio of the low-affinity and high-affinity dissociation constants [KL/KH] 140 +/- 7.4 versus 66 +/- 4.3, p less than 0.001). There were negative correlations between the KL/KH value and the dose of isoproterenol required to decrease MAP by 20 torr (p less than 0.02) and between the KL/KH value and the product of the hormone receptor and MAP (p less than 0.01). However, the patients could be subdivided into a group who could mount a nearly normal hormone receptor times MAP response on standing (group 1A), and a group who could not (group 1B). The group 1A patients had elevated plasma norepinephrine responses associated with milder beta 2-adrenergic receptor supercoupling, whereas group 1B patients had essentially no orthostatic plasma norepinephrine response and had much higher KL/KH values. Thus, though a state of biochemical supersensitivity existed in both patient subgroups, diminished catecholamine exposure was associated, as expected, with beta 2-adrenergic hypersensitivity in group 1B, whereas there was no diminution of catecholamine exposure in the beta 2-adrenergic hypersensitivity observed in group 1A patients.     

A pilot study indicating that bradykinin B2 receptor antagonism attenuates protamine-related hypotension after cardiopulmonary bypass

BACKGROUND: The administration of protamine to patients who received heparin during cardiopulmonary bypass (CPB) induces hypotension. Protamine inhibits the carboxypeptidase N-mediated degradation of bradykinin, a peptide that causes vasodilation and tissue-type plasminogen activator (t-PA) release. This study tests the primary hypothesis that blocking the bradykinin B(2) receptor would attenuate protamine-related hypotension. METHODS: We conducted a prospective, double-blind, randomized study in 16 adult male patients undergoing elective cardiac surgery requiring CPB and taking an angiotensin-converting enzyme (ACE) inhibitor preoperatively, because ACE inhibition increases bradykinin concentrations during CPB. Subjects were randomized to receive either saline solution (N = 8) or the bradykinin B(2) receptor antagonist HOE 140 (100 mug/kg, N = 8) before the administration of protamine. Mean arterial pressure (MAP) and t-PA activity were measured intraoperatively and before and after protamine administration. RESULTS: Protamine administration caused a significant increase in bradykinin concentrations in the saline solution group (from 6.0 +/- 1.3 to 10.0 +/- 1.6 fmol/mL, P = .043), as well as the HOE 140 group (from 6.5 +/- 1.8 to 14.3 +/- 4.6 fmol/mL, P = .042). Protamine significantly decreased MAP in the saline solution group (from 69.8 +/- 4.4 mm Hg to a mean individual nadir of 56.1 +/- 2.6 mm Hg, P = .031), but bradykinin receptor antagonism blunted this effect (from 74.3 +/- 3.7 mm Hg to a mean individual nadir of 69.6 +/- 1.2 mm Hg in the HOE 140 group, P = .545). Hence, during protamine infusion, MAP was significantly lower in the saline solution group compared with the HOE 140 group (P = .002). t-PA activity decreased significantly during administration of HOE 140 (from 3.59 +/- 0.31 to 1.67 +/- 0.42 IU/mL, P = .001) but not during saline solution (from 2.12 +/- 0.48 to 1.44 +/- 0.36 IU/mL, P = .214). Similarly, t-PA activity decreased significantly during protamine administration in the HOE 140 group (from 1.67 +/- 0.42 to 0.77 +/- 0.26 IU/mL, P = .038) but not in the saline solution group (from 1.44 +/- 0.36 to 0.99 +/- 0.26 IU/mL, P = .132). CONCLUSION: Increased bradykinin contributes to protamine-related hypotension through its B(2) receptor in ACE inhibitor-treated patients.     

Paradoxical withdrawal of reflex vasoconstriction as a cause of hemodialysis-induced hypotension.

Acute hypotension is an important complication of hemodialysis, but the underlying mechanisms remain poorly understood. Because hemorrhage-induced hypovolemia can trigger a sudden decrease in sympathetic activity resulting in bradycardia and vasodilation, we hypothesized that hemodialysis-induced hypovolemia also can trigger the same type of vasodepressor reaction, which would exacerbate the volume-dependent fall in blood pressure. We therefore measured blood pressure, vascular resistance, and sympathetic nerve activity (intraneural microelectrodes) during sessions of maintenance hemodialysis in 7 patients with and 16 patients without a history of hemodialysis-induced hypotension. During hemodialysis, blood pressure at first remained unchanged as calf resistance increased in both hypotension-resistant (from 37 +/- 4 to 49 +/- 5 U, P < 0.05) and hypotension-prone (from 42 +/- 6 to 66 +/- 12 U, P < 0.05) patients; sympathetic activity increased comparably in the subset of patients in whom it could be measured. With continued hemodialysis, calf resistance and sympathetic activity increased further in the hypotension-resistant patients, but in the hypotension-prone patients the precipitous decrease in blood pressure was accompanied by decreases in sympathetic activity, vascular resistance, and heart rate as well as symptoms of vasodepressor syncope. On an interdialysis day, both groups of patients increased vascular resistance normally during unloading of cardiopulmonary baroreceptors with lower body negative pressure and increased heart rate normally during unloading of arterial baroreceptors with infusion of nitroprusside. These findings indicate that in a group of hemodialysis patients without diabetes or other conditions known to impair autonomic reflexes, hemodialysis-induced hypotension is not caused by chronic uremic impairment in arterial or cardiopulmonary baroreflexes but rather by acute, paradoxical withdrawal of sympathetic vasoconstrictor drive producing vasodepressor syncope.     

Large-pore hemodialysis in acute endotoxin shock

OBJECTIVE: This study was undertaken to test the hypothesis that hemodialysis with a large-pore membrane would improve heart function during acute endotoxin shock. SETTING: Large animal laboratory. DESIGN: Eighteen mongrel dogs were instrumented to measure left ventricular maximum end-systolic elastance (left ventricular maximum elastance at end systole), cardiac output, circumflex artery blood flow, and myocardial mechanical efficiency (CO x MAP/MVO2, where CO is cardiac output, MAP is mean arterial pressure, and MVO2 is myocardial oxygen consumption). Plasma catecholamine concentrations were determined by high-performance liquid chromatography. Endotoxin shock was induced by infusing 5.0 microg/kg/min of Escherichia col 0127:B8 endotoxin in the portal vein for 60 mins, followed by 2.0 microg/kg/min of constant infusion. Control dogs (n = 6) received 4.0 mL/kg/min of saline; hemodialysis dogs (n = 6) underwent venovenous hemodialysis in 50-min intervals using a polysulfone filter (1.2 m2; mean pore size, 0.50 nm; blood flow rate, 400 mL/min; ultrafiltrate, "zero-balanced"); shams (n = 5) were treated identically to hemodialysis dogs, except that no convective dialysis was performed. A fourth group (n = 6) was treated with dopamine (5.0-7.0 microg/kg/min, optimal dose for contractile increase based on dose-response studies). MEASUREMENTS AND MAIN RESULTS: After 2 hrs of treatment, left ventricular maximum elastance at end systole increased and was unchanged in controls (30 +/- 5 mm Hg/mm) and shams (24 +/- 6 mm Hg/mm) compared with basal control. Hemodialysis treatment increased contractility (53 +/- 4 mm Hg/mm), as did dopamine treatment (54 +/- 7 mm Hg/mm). Endotoxin shock reduced mechanical efficiency to 45% of basal control; with hemodialysis treatment, left ventricular efficiency returned to 64% of basal control measurement, compared with 49% with dopamine treatment. During treatment, myocardial glucose uptake was increased with hemodialysis compared with other groups. No difference was observed among groups for left ventricular end-diastolic pressures or dimensions, or catecholamine concentrations. CONCLUSIONS: Large-pore hemodialysis increased left ventricular contractility to a similar degree as dopamine and provided a marginal improvement in myocardial glucose uptake and mechanical efficiency.     

Plasma volume regulation in patients with progressive autonomic failure during changes in salt intake or posture

Blood pressure in patients with progressive autonomic failure falls during salt restriction or orthostasis. We contrasted the regulation of plasma volume in patients with progressive autonomic failure with that of controls to determine whether hypovolemia contributes to this hypotension. When sitting, the plasma volume (measured from distribution of human serum albumin) was normal. During 1 week of low Na+ intake, patients with progressive autonomic failure lost three times as much body weight as controls; however, changes in plasma volume were strictly comparable. Therefore, the extra fluid lost in the patients must have derived primarily from the interstitial space. During alteration in Na+ intake, mean blood pressure values were closely related to plasma volume in the patients (r = 0.80, p less than 0.01) but not in controls. Changes in plasma volume in the head-up tilt position were assessed from the hematocrit values. During tilting, the blood pressure in controls was unchanged, but their plasma volume fell by 10.3% +/- 1.8% (p less than 0.001). In contrast, the mean blood pressure of the patients with progressive autonomic failure fell by 40 +/- 6 mm Hg; yet, their plasma volume was unchanged. Thus, in progressive autonomic failure, plasma volume measured during sitting is normal, but dynamic regulation of plasma volume during salt restriction or orthostasis is abnormal and hypovolemia is offset by partitioning of interstitial fluid into the plasma. Also, because the blood pressure is unusually dependent on volume, this fluid redistribution could be an important defense against severe hypotension in patients lacking cardiovascular reflex control.     

Effects of perfusion pressure on tissue perfusion in septic shock

OBJECTIVE: To measure the effects of increasing mean arterial pressure (MAP) on systemic oxygen metabolism and regional tissue perfusion in septic shock. DESIGN: Prospective study. SETTING: Medical and surgical intensive care units of a tertiary care teaching hospital. PATIENTS: Ten patients with the diagnosis of septic shock who required pressor agents to maintain a MAP > or = 60 mm Hg after fluid resuscitation to a pulmonary artery occlusion pressure (PAOP) > or = 12 mm Hg. INTERVENTIONS: Norepinephrine was titrated to MAPs of 65, 75, and 85 mm Hg in 10 patients with septic shock. MEASUREMENTS AND MAIN RESULTS: At each level of MAP, hemodynamic parameters (heart rate, PAOP, cardiac index, left ventricular stroke work index, and systemic vascular resistance index), metabolic parameters (oxygen delivery, oxygen consumption, arterial lactate), and regional perfusion parameters (gastric mucosal Pco2, skin capillary blood flow and red blood cell velocity, urine output) were measured. Increasing the MAP from 65 to 85 mm Hg with norepinephrine resulted in increases in cardiac index from 4.7+/-0.5 L/min/m2 to 5.5+/-0.6 L/min/m2 (p < 0.03). Arterial lactate was 3.1+/-0.9 mEq/L at a MAP of 65 mm Hg and 3.0+/-0.9 mEq/L at 85 mm Hg (NS). The gradient between arterial P(CO2) and gastric intramucosal Pco2 was 13+/-3 mm Hg (1.7+/-0.4 kPa) at a MAP of 65 mm Hg and 16+/-3 at 85 mm Hg (2.1+/-0.4 kPa) (NS). Urine output at 65 mm Hg was 49+/-18 mL/hr and was 43+/-13 mL/hr at 85 mm Hg (NS). As the MAP was raised, there were no significant changes in skin capillary blood flow or red blood cell velocity. CONCLUSIONS: Increasing the MAP from 65 mm Hg to 85 mm Hg with norepinephrine does not significantly affect systemic oxygen metabolism, skin microcirculatory blood flow, urine output, or splanchnic perfusion.     

脑死亡患者实施呼吸暂停试验安全性的临床研究

目的观察深昏迷脑死亡和非脑死亡患者传统呼吸暂停试验时严重并发症的发生情况,探索有效的预防措施。方法收集可疑脑死亡病例15例,采用传统呼吸暂停试验,试验前补足前负荷或给予小剂量去甲肾上腺素(NE)维持循环。于试验前、吸纯氧后、脱机4min、脱机6~8min以及重新上机后5min进行动脉血气分析,记录血流动力学参数以及NE用量,试验前及试验结束后测定血乳酸浓度。结果15例患者中,14例呼吸暂停试验结果为阳性,1例阴性。阳性患者脱机后8min内动脉血二氧化碳分压(PaCO2)显著上升〔>60mm Hg(1mm Hg=0.133kPa),P<0.01〕,pH值下降(P<0.05),但动脉血氧分压(PaO2)保持在100mm Hg以上;心率、平均动脉压(MAP)轻度下降,但差异无显著性;与基础值比较,平均肺动脉压(PAP)显著升高(P<0.05)。而试验结果阴性患者脱机后心率加快,血压上升,出现自主呼吸,重新给予机械通气后循环恢复平稳。试验过程中无严重心律失常发生。11例进行呼吸暂停试验的患者给予NE维持循环(NE组),NE泵入剂量〔0.10~0.60μg·kg-1·min-1,平均(0.23±0.17)μg·kg-1·min-1,始终无改变〕。余4例患者(无NE组)未用任何血管活性药物。使用或未使用NE的患者MAP、PAP和肺动脉楔压(PAWP)变化趋势基本一致,HR、MAP、PAWP下降,PAP则升高,但两组间比较差异均无显著性。与基础值比较,试验结束时患者血乳酸浓度无明显变化〔(1.41±0.05)mmol/L比(1.47±0.07)mmol/L〕。结论传统呼吸暂停试验能保证患者良好的氧合状态,对非脑死亡患者引起低血压的风险更小。在补足前负荷基础上,给予小剂量NE进行循环支持治疗,能有效防止脑死亡患者呼吸暂停试验时严重低血压的发生。     

Heart function after severe hemorrhagic shock

OBJECTIVE: Test whether brief deep hemorrhagic hypotension or prolonged moderate hemorrhagic hypotension impairs intrinsic heart function. METHODS: Pentobarbital-anesthetized, non-anticoagulated rats were cannulated via the carotid artery. This study focuses on three main groups: 1) hemorrhage to a mean arterial blood pressure (MAP)=25 mm Hg for 1 h (1 h severe shock), 2) hemorrhage to MAP=40 mm Hg for 3 h (3 h moderate shock), 3) no hemorrhage (control). Hearts were either freeze-clamped in-situ for tissue analysis (n=6 per group) or were removed to study in vitro cardiac function and efficiency using a working heart perfusion (n=12 per group, glucose (11 mM)/palmitate (0.4 mM), 3% BSA buffer). Following perfusion, hearts were freeze-clamped and analyzed for free CoA, acetyl-, succinyl-, and malonyl-CoA, ATP content and for TNF-alpha content. RESULTS: Isolated working hearts obtained following 1 h of severe shock generated 20% less hydraulic work than hearts obtained from control rats or rats subjected to 3 h of moderate shock. The cardiac efficiency (work/O2 consumption) was also significantly reduced with 1 h severe shock (0.76 +/- 0.07 after 15 min perfusion) versus control (0.96 +/- 0.06) or 3 h prolonged shock (1.10 +/- 0.09). Myocardial Co-A ester, ATP and TNF-alpha concentrations were not different between control and shocked hearts, although TNF-alpha concentrations increased significantly in all hearts during ex vivo perfusion. CONCLUSIONS: Depth of hypotension is more important than duration in causing intrinsic cardiac dysfunction. This post-hemorrhagic cardiac dysfunction is not a result of substrate limitation to the heart, nor myocardial TNF-alpha accumulation, but is more likely a result of impaired transfer of energy from molecular oxygen into external cardiac work.     

Hemodynamic benefit of maintaining atrioventricular synchrony during cardiac pacing in critically ill patients

OBJECTIVE: To determine the hemodynamic effects of maintaining atrioventricular synchrony during emergency cardiac pacing in critically ill patients. DESIGN: Prospective, within patient double-blind study. SETTING: ICU or coronary care unit patients in a university hospital. PATIENTS: Forty (23 cardiac surgery, ten acute myocardial infarction, and seven general intensive care) seriously ill patients with severe symptomatic bradycardia. INTERVENTION: Initial randomization of patients to receive either a pacing mode where atrioventricular synchronization was maintained (atrioventricular pacing: atrial demand, atrioventricular sequential, atrioventricular universal) or a mode of pacing where atrioventricular synchrony was not preserved (ventricular demand pacing). MEASUREMENTS and MAIN RESULTS: The cardiac output increased from a mean of 4.5 +/- 1.7 L/min (95% confidence intervals: 4.0 to 5.0 L/min) during ventricular demand pacing to 5.3 +/- 1.7 L/min (95% confidence intervals: 4.9 to 5.9 L/min) during atrioventricular pacing (p less than .0001) despite trivial decreases in CVP from 14 +/- 4 mm Hg (95% confidence intervals: 13 to 15 mm Hg) to 13 +/- 5 mm Hg (95% confidence intervals: 12 to 15 mm Hg) and pulmonary artery occlusion pressure from 18 +/- 5 mm Hg (95% confidence intervals: 16 to 20 mm Hg) to 17 +/- 5 mm Hg (95% confidence intervals: 15 to 18 mm Hg). At the same time, mean arterial pressure (MAP) increased from 74 +/- 15 mm Hg (95% confidence intervals: 64 to 79 mm Hg) to 83 +/- 15 mm Hg (95% confidence intervals: 80 to 88 mm Hg) and left ventricular stroke work index from 22 +/- 10 g.m/m2 (95% confidence intervals: 19 to 25 g.m/m2) to 30 +/- 11 g.m/m2 (95% confidence intervals: 26 to 33 g.m/m2). There was no significant change in mean pulmonary artery pressure, pulmonary vascular resistance index, or systemic vascular resistance index. CONCLUSION: When cardiac pacing is required in critically ill patients, maintaining atrioventricular synchrony increases stroke volume, cardiac output, and MAP apparently with minimal effects on preload and afterload.     

Transcutaneous PO2 monitoring during sodium nitroprusside infusion

To determine the effect of vasodilator-induced hypotension on the relationship between transcutaneous PO2 (PtcO2) and PaO2, six mongrel dogs and 20 patients were monitored before and during infusion of sodium nitroprusside (SNP), with PtcO2 sensors heated to 45 degrees C. First, SNP infusion was used to lower the mean arterial pressure (MAP) of anesthetized dogs, in steps of approximately 25%, to 49 +/- 3 (SD) mm Hg. There were no significant changes in cardiac output, oxygen consumption, PtcO2, PaO2, or PtcO2 index (PtcO2/PaO2). Twenty patients were monitored during general anesthesia. Fifteen patients were being treated for acute hypertension with SNP, and in five patients hypotension was induced with SNP to minimize blood loss. There was a significant decrease in MAP, PaO2, and PtcO2, and a significant increase in alveolar-arterial PO2 difference during SNP infusion. PtcO2 index did not change significantly from its preinfusion value in either group.     

Spectrum of autonomic cardiovascular neuropathy in diabetes

OBJECTIVE: Diabetic patients with incapacitating orthostatic hypotension can have either a "hyperadrenergic" or "hypoadrenergic" presentation. Although the latter is related to overt autonomic neuropathy, the former is proposed to be explained by appropriate autonomic responses. We hypothesize, however, that both conditions are part of a spectrum of autonomic dysfunction. RESEARCH DESIGN AND METHODS: We studied 16 consecutive diabetic patients with preserved renal function referred for incapacitating orthostatic hypotension and characterized their autonomic and neurohumoral cardiovascular regulation. RESULTS: Six patients had a hyperadrenergic orthostatic response: systolic blood pressure fell 42 +/- 15 mmHg, heart rate increased 20 +/- 3 bpm, and plasma norepinephrine increased from 340 +/- 80 to 910 +/- 100 pg/ml. Ten patients had a hypoadrenergic response: systolic blood pressure fell 78 +/- 5 mmHg, heart rate increased only 7 +/- 3 bpm, and norepinephrine increased only from 130 +/- 28 to 230 +/- 40 pg/ml. Vagal (sinus arrhythmia, Valsalva ratio) and sympathetic (response to hyperventilation, postprandial hypotension) responses were impaired in both groups, but to a greater extent in the hypoadrenergic group. Notwithstanding severe orthostatic hypotension, the postural increase in plasma renin was blunted in both groups, more so in the hypoadrenergic group. Despite preserved renal function, patients had mild anemia due to impaired erythropoietin release, as seen in primary cases of autonomic failure. CONCLUSIONS: Our results suggest that diabetic patients presenting with hyperadrenergic orthostatic hypotension have an initial stage of autonomic neuropathy, with overtly abnormal vagal function and early signs of sympathetic impairment. Furthermore, altered renin response can contribute to the patients' orthostatic hypotension.     

Differential blood pressure and hormonal effects after glucose and xylose ingestion in chronic autonomic failure

1. To investigate whether carbohydrate contributes to postprandial hypotension in autonomic failure, the cardiovascular, biochemical and hormonal effects of oral glucose and an iso-osmotic solution of oral xylose were studied on separate occasions in six patients with chronic autonomic failure. The effects of oral glucose were also studied in eight normal subjects. 2. In the patients oral glucose lowered blood pressure substantially (-34 +/- 7% at 60 min, area under curve -24.9 +/- 3.5%, P less than 0.001) and for a prolonged period (-25 +/- 4% at 120 min). Plasma noradrenaline levels did not change. In the normal subjects blood pressure was unchanged and plasma noradrenaline rose, suggesting a compensatory increase in sympathetic nervous activity. 3. In the patients xylose caused a smaller and more transient fall in blood pressure (-15 +/- 6% at 90 min, area under curve -8.9 +/- 4%, P less than 0.05) with a non-significant elevation in packed cell volume (36.7 +/- 1.8 to 38.2 +/- 1.8). It was therefore unclear if xylose was exerting osmotic effects within the bowel which contributed to the small blood pressure fall. Packed cell volume did not change in either the patients or normal subjects after glucose. 4. In the patients and normal subjects plasma insulin rose after glucose. Insulin levels were unchanged after xylose. Levels of pancreatic polypeptide and neurotensin, a potential vasodilator, rose in the patients only. The latter rose to a similar extent after both glucose and xylose, making it unlikely that neurotensin alone accounted for the hypotension. 5. These studies indicate that the carbohydrate components of a meal, and in particular those causing insulin release, contribute to postprandial hypotension in patients with autonomic failure.     

A randomized,placebo-controlled,phase 2 study of the efficacy and safety of droxidopa in patients with intradialytic hypotension

Introduction: Intradialytic hypotension (IDH) is the most common complication of hemodialysis (HD), and it plays a significant role in the morbidity and mortality associated with maintenance HD. Methods: This was a placebo-controlled, parallel-group study evaluating efficacy and safety of droxidopa in improving intradialytic blood pressure (BP) responses in 85 adults with end-stage renal disease (ESRD) and prone to IDH. Following screening and baseline periods, patients received 400 mg or 600 mg droxidopa, or placebo, orally 1 hour before HD for 4 weeks. Primary outcome endpoint was the change between baseline and last 2 treatment weeks in average mean arterial pressure (MAP) during HD. Also assessed were changes from baseline in systolic BP (SBP) and diastolic BP (DBP) during and after HD; number of hypotension-induced interventions and symptoms; and adverse events. Results: Increase in droxidopa intra-HD MAP were not significantly different from placebo, although droxidopa groups showed significant improvements in mean SBP after HD of +4.8 ± 11.6 mm Hg (600-mg) and +3.4 ± 13.1 (400-mg) compared with –4.4 ± 17.9 mm Hg in placebo, and the drop seen in mean nadir SBP pre- to intra-HD was also reduced. Changes in mean DBP pre- and post-HD, changes in mean nadir SBP post-HD, or intra-HD SBP were not significant over the treatment period. HD terminations decreased 5-fold in the 600-mg group and 2-fold in the 400-mg group, whereas the number of discontinuations stayed unchanged in the placebo group. Overall, treatment with 600-mg or 400-mg droxidopa was well tolerated in this population. Conclusion: These data suggest that droxidopa may have a role in reducing IDH complications in patients with ESRD on chronic HD.     

Coronary angiography during acute myocardial infarction in dogs: comparison of the hemodynamic effects of ionic and nonionic contrast media

We compared the hemodynamic effects during coronary angiography of three nonionic contrast media, iopamidol, iohexol, and ioversol, with each other as well as with the standard ionic contrast medium containing 66% diatrizoate meglumine and 10% diatrizoate sodium (Hypaque-76) in the presence of a left anterior descending coronary artery occlusion in dogs. In 13 opened-chest anesthetized dogs, we recorded the maximal change in left ventricular systolic pressure (LVSP), mean aortic pressure (MAP), left ventricular diastolic pressure (LVDP) and rate of rise in left ventricular pressure (LV dp/dt) during left main coronary artery injections of 10 ml each of Hypaque-76, iopamidol, iohexol, and loversal 1 hour after left anterior descending coronary artery occlusion. The changes in LVSP and MAP were, respectively, -29 +/- 12 mm Hg and -21 +/- 11 mm Hg with Hypaque-76, 3 +/- 6.6 mm Hg and -0.2 +/- 3.6 mm Hg with iopamidol, 4.8 +/- 8.6 mm Hg and 0.5 +/- 4 mm Hg with iohexol, and -0.8 +/- 6 mm Hg and -1.5 +/- 33 mm Hg with ioversal (p less than 0.001). The change in LVDP was 5.4 +/- 4.4 mm Hg with Hypaque-76 but -1.5 +/- 3.1 mm Hg with iopamidol, -1.7 +/- 2.4 mm Hg with iohexol, and -0.5 +/- 2.5 mm Hg with ioversol (p less than 0.001). The LV dp/dt decreased 682 +/- 318 mm Hg/sec with Hypaque-76, but increased 412 +/- 297 mm Hg/sec with iopamidol, 350 +/- 214 mm Hg/sec with iohexol, and 293 +/- 191 mm Hg/sec with ioversol (p less than 0.001). Thus, each nonionic agent produced significantly fewer hemodynamic abnormalities than Hypaque-76. There was no significant difference between any of the nonionic agents on any hemodynamic parameter. These agents may be preferable in patients with acute myocardial infarction or significantly impaired myocardial function.     

Cardiovascular responses and postexercise hypotension after arm cycling exercise in subjects with spinal cord injury

OBJECTIVE: To examine postexercise hypotension and contributing factors in subjects with spinal cord injury (SCI). DESIGN: Prospective clinical research study. SETTING: Rehabilitation center. PARTICIPANTS: Subjects with chronic cervical-level (n=19) and thoracic-level (n=8) SCI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjects underwent graded arm-cycling with electrocardiogram and oxygen uptake monitoring to exhaustion. Heart rates and blood pressures were measured before and after exercising. Injury to motor and sensory pathways was determined by American Spinal Injury Association grade, and to autonomic pathways by sympathetic skin responses (SSRs) (n=16). RESULTS: Resting blood pressures and heart rates were lower in cervical than thoracic SCI (mean arterial pressure [MAP]: cervical, 76.6+/-2 mmHg; thoracic, 93.5+/-3 mmHg; P<.001). Following exercise, heart rate responses were greater in thoracic than cervical SCI; MAP increased in thoracic SCI (8.4+/-5 mmHg) and markedly decreased in cervical SCI (-9.3+/-2 mmHg) (P<.001). No subject had significant electrocardiographic abnormalities at rest or during exercise. There were correlations between SSR and heart rate and blood pressure responses to exercise; the correlation between the SSR and blood pressure response was due to an interaction between the heart rate and blood pressure responses. CONCLUSIONS: Abnormal cardiovascular responses to exercise and transient postexercise hypotension were common in cervical, but not thoracic SCI. This may be partly related to loss of descending sympathetic nervous control of the heart and vasculature following high SCI.     

血透中进餐对终末期糖尿病肾病患者血压的影响

目的探讨终末期糖尿病肾病(ESDN)患者血液透析(HD)中进餐时血压的变化与意义。方法将20例ESDN患者1686例次维持性HD,按HD中进餐与否分为:进餐组(A组)及非进餐组(B组),并与20例非ES-DN患者1620例次HD也分为:进餐组(C组)及非进餐组(D组)作对照,比较四组平均动脉压(MAP)变化并结合血糖(BG)水平进行分析。结果低血压发生率:A组(339/843,40.2%)B组(265/843,31.4%),C组(251/810,29.8%)D组(167/810,20.6%),(P0.005),B、C两组差异无显著意义;A组伴低血糖(31例次)者MAP明显高于无低血糖(308例次)者;B组伴低血糖(45例次)者的MAP与无低BG(220例次)者相当。A、B两组中伴低血糖者MAP与BG均呈正相关(P0.001)余各组MAP与BG无相关(P0.05)。结论在HD中进餐可能增加症状性低血压的发生率,尤以ESDN患者为甚。在HD中伴低血糖的ESDN患者更易发生低血压。在透析中进餐,可能预防伴低血糖的ESDN患者者所发生的低血压;对无低血糖反应的ESDN患者所发生的低血压,则尽量避免进餐。     

Acute hemodynamic and humoral effects of metoclopramide on blood pressure control improvement in subjects with diabetic orthostatic hypotension

Metoclopramide (MCP), a dopaminergic antagonist, is effective in postural hypotension, but the mechanisms of action have not been well defined. We studied responses of mean arterial pressure (MAP), heart rate, cardiac output (CO), and total peripheral resistance (TPR) after 5 min of increasing degrees of head tilt (15 degrees to 90 degrees) before and after MCP (20 mg IV) in seven subjects with diabetic postural hypotension. Plasma renin activity (PRA) and plasma aldosterone levels (PA) were determined at each degree of tilt; responses to the cold pressor test were also assessed before and after MCP. Before MCP, the maximal degree of tilt tolerated was 75 degrees, while after MCP four subjects were able to support 90 degrees tilt. At 45 degrees tilt, the decreases in MAP were smaller after than before MCP (-7.6 +/- 3.3 and -28.1 +/- 8.5 mm Hg; means +/- SE). This was associated with responses of TPR to tilt after (from 18.6 +/- 2.6 to 24.0 +/- 3.9 arbitrary units [AU]) but not before (from 22.9 +/- 4.0 to 25.6 +/- 4.5 AU) MCP. Reductions in CO were of the same order before and after MCP. PRA responded to tilt better after than before MCP. Supine PA levels increased with MCP (delta PA = 5.4 +/- 0.7 ng/dl), but its response to tilt was unaltered. There were significant rises in MAP and HR during the cold pressor test after but not before MCP. Our data suggest that vasoconstriction is the main mechanism of MCP improvement in blood pressure response to an orthostatic stimulus in diabetic postural hypotension, possibly because of its antidopaminergic property.     

生物电阻抗技术监测血液透析时细胞外液量及其临床价值

目的：采用生物电阻抗技术监测血液透析过程中患者细胞外液量（ECV）的变化,以指导调整透析患者于体质量,透预防析中低血压或难治性高血压。方法：100例维持性血透患者,透析时间4～112（58．67±31．54）个月,根据临床表现分为正常血压组、症状性低血压组和难治性高血压组。采用生物电阻抗仪测定患者血透时的细胞外液量（ECV）％、细胞内液量（ICV）％、ECV／ICV的变化。观察透析过程中患者心率、呼吸、血压、超滤量和超滤率的变化,比较3组各项指标的变化,并分析各参数同的相互关系。结果：透析过程中随超滤量增加,超滤脱水率逐渐下降,3组中症状性低血压组超滤量最大,超滤率最高;难治性高血压组超滤量最小,超滤率最低。透析前3组ECV％、ECV／ICV均高于正常对照组,其中难治性高血压组最高。透析后3组ECV％、ECV/ICV均。显著下降,但难治性高血压组仍显著高于正常对照组。透析后3组ICV％显著升高,但仍低于正常对照组。透析时症状性低血压组随ECV下降,平均动脉压（MAP）明显下降,两者呈显著正相关（r=0．914,P〈0．001）。难治性高血压组随ECV下降,MAP逐渐升高,两者呈现负相关（r=-0．782,P=0．035）。对5例低血压和7例高血压患者在生物电阻抗监测ECV的指导下分别上调或下调干体质量后血压得到有效控制。结论：生物电阻抗监测ECV有助于指导调整干体质量,确定合适的超滤量,预防透析中低血压和控制高血压。