Acute Decrease In Blood Pressure Research Articles

Effects of dynamic resistance training on postexercise hypotension and its mechanisms in hypertensive men.

A possible chronic effect of exercise training is the attenuation of the acute decrease in blood pressure (BP) observed after the execution of a session of exercise [i.e. called postexercise hypotension (PEH)]. However, there are few empirical data regarding this issue, and the possible mechanisms involved in this blunted response have not been studied. The study aimed to evaluate the effects of dynamic resistance training (DRT) on PEH and its systemic, vascular, and autonomic mechanisms. Data from 16 middle-aged treated hypertensive men who underwent DRT (eight exercises, 50% of 1RM, three sets until moderate fatigue) three times/week for 10 weeks were analyzed. Before and after the training period, the participants underwent an experimental session in which BP (auscultation), systemic hemodynamics (CO2 rebreathing), vascular function (duplex ultrasound), and cardiovascular autonomic modulation (spectral analysis of heart rate and BP variabilities) were assessed before and after a session of DRT. DRT reduced preexercise systolic BP and mitigated the systolic PEH that occurred before but not after the training period (P = 0.017). DRT did not change the diastolic PEH that occurred with similar magnitude before and after the training period (P = 0.024). DRT did not change the PEH mechanisms, except for cardiac sympathovagal balance that increased significantly more after the session of DRT conducted in the posttraining evaluation (P = 0.017). In medicated hypertensive men, 10 weeks of DRT decreased preexercise systolic BP, abolished systolic PEH, and induced a greater increase in postdynamic resistance exercise sympathovagal balance.

Can blood pressure decrease after maximal exercise test predict the blood pressure lowering effect of aerobic training in treated hypertensive men?

The acute decrease in blood pressure (BP) observed after a session of exercise (called post-exercise hypotension) has been proposed as a tool to predict the chronic reduction in BP induced by aerobic training. Therefore, this study investigated whether post-exercise hypotension observed after a maximal exercise test is associated to the BP-lowering effect of aerobic training in treated hypertensives. Thirty hypertensive men (50 ± 8 years) who were under consistent anti-hypertensive treatment underwent a maximal exercise test (15 watts/min until exhaustion), and post-exercise hypotension was determined by the difference between BP measured before and at 30 min after the test. Subsequently, the patients underwent 10 weeks of aerobic training (3 times/week, 45 min/session at moderate intensity), and the BP-lowering effect of training was assessed by the difference in BP measured before and after the training period. Pearson correlations were employed to evaluate the associations. Post-maximal exercise test hypotension was observed for systolic and mean BPs (-8 ± 6 and -2 ± 4 mmHg, all P < 0.05). Aerobic training reduced clinic systolic/diastolic BPs (-5 ± 6/-2 ± 3 mmHg, both P < 0.05) as well as awake and 24 h mean BPs (-2 ± 6 and -2 ± 5 mmHg, all P < 0.05). No significant correlation was detected between post-exercise hypotension and the BP-lowering effect of training either for clinic or ambulatory BPs (r values ranging from 0.00 to 0.32, all p > 0.05). Post-exercise hypotension assessed 30 min after a maximal exercise test cannot be used to predict the BP-lowering effect of aerobic training in treated hypertensive men.

Influence of Load Intensity on Postexercise Hypotension and Heart Rate Variability after a Strength Training Session.

The purpose of this study was to compare blood pressure and heart rate variability (HRV) responses in trained men after strength training (ST) sessions with loads of 60, 70, and 80% of a 1 repetition maximum (1RM). Eleven men (age: 26.1 ± 3.6 years; body mass: 74.1 ± 8.1 kg; height: 172.0 ± 4.0 cm; body mass index: 25.0 ± 1.96 kg·m(-2); %G: 18.3 ± 6.4) with at least 6-month ST experience participated in this study. After assessment of 1RM loads for the bench press (BP), lat pull-down (LPD), shoulder press (SP), biceps curl (BC), triceps extension (TE), leg press (LP), leg extension (LE), and leg curl (LC), subjects performed 3 experimental sessions in random order. During each experimental session, subjects performed 3 sets of 8-10 repetitions at 60, 70, or 80% of 1RM loads, with 2-minute rest intervals between sets and exercises. All experimental sessions were performed in the following exercise order: BP, LPD, SP, BC, TE, LP, LE, and LC. Before and for 1 hour after each experimental session, blood pressure and HRV were tracked. The results demonstrated a greater duration of postexercise hypotension (PEH) after the 70% of 1RM session vs. the 60 or 80% of 1RM session. These results indicate that the load/volume associated with completion of 8-10 repetitions at 70% of 1RM load may provide the best stimulus for the PEH response when compared with training with a 60 or 80% of 1RM loads. In conclusion, strength and conditioning professionals may prescribe exercises with 60, 70, and 80% of 1RM loads if the intent is to elicit an acute decrease in blood pressure after an ST session; however, 70% of 1RM provides a longer PEH.

Inner ocular blood flow responses to an acute decrease in blood pressure in resting humans

Whether inner ocular vessels have an autoregulatory response to acute fluctuations in blood pressure is unclear. We tried to examine the validity of acute hypotension elicited by thigh-cuff release as to assess the dynamic autoregulation in the ocular circulation. Blood flow velocity in the superior nasal and inferior temporal retinal arterioles, and in the retinal and choroidal vasculature were measured with the aid of laser speckle flowgraphy before and immediately after an acute decrease in blood pressure in 20 healthy subjects. Acute hypotension was induced by a rapid release of bilateral thigh occlusion cuffs that had been inflated to 220 mmHg for 2 min. The ratio of the relative change in retinal and choroidal blood flow velocity to the relative change in mean arterial blood pressure (MAP) was calculated. Immediately after cuff release, the MAP and blood flows in the all ocular target vessels decreased significantly from the baseline values obtained before thigh-cuff release. The ratio of the relative change in inner ocular blood flow velocity to that in the MAP exceeded 1% / %mmHg. An explicit dynamic autoregulation in inner ocular vessels cannot be demonstrated in response to an acute hypotension induced by the thigh-cuff release technique.

Hipotensão pós-exercício induzida por treinamento aeróbio, de força e concorrente: aspectos metodológicos e mecanismos fisiológicos

Evidence indicates that chronic reduction in blood pressure (BP) due to physical exercise depends on the acute decrease in BP after a training bout, phenomenon referred as post-exercise hypotension (PEH). This study reviews research on PEH after acute aerobic, strength and concurrent exercise and its potential underlying mechanisms. The PEH has been observed following different exercise modalities in both normotensive and hypertensive subjects. However, the optimal dose of aerobic exercise [i.e. relationship between intensity, duration, mode and form of execution] and strength training [i.e. relationship between intensity, volume and muscle mass involved] to maximize its occurrence remains unclear. Questions also persist with regard to the physiological pathways of PEH, which seem to be different in strength and aerobic exercise. Central and local mechanisms associated to decreased cardiac output (CO) and peripheral vascular resistance (PVR) are frequently mentioned in the literature. Mechanisms underlying PEH after aerobic exercise seemto include both central [i.e. decreased activity sympathetic nerve] and peripheral factors[i.e. vasodilation sustained by nitric oxide releasing, prostaglandins and histamine receptors]. On the other hand, after strength or concurrent training, the PEH seems to bemostly related to a decrease in CO and systolic volume, in response to a decrease in myocardial perfusion during exercise due to compression of vessels by sequential muscle contraction.

Baroreflex sensitivity is associated with blood pressure transients in young men but not young women

Baroreflex sensitivity is calculated from the slope of the relationship between blood pressure and muscle sympathetic nerve activity (MSNA) or cardiac R‐R interval. The magnitude of decrease in blood pressure during a vasoactive drug bolus (i.e. modified Oxford) to test the baroreflex may be associated with the calculated baroreflex sensitivity (BRS) slope. We investigated whether the cardiac or sympathetic BRS are associated with the acute decrease in blood pressure during a modified Oxford in young healthy men and women. Forty‐five women (27 ± 1 yrs, BMI 22.9 ± 0.3 kg/m2) and 30 men (27 ± 1 yrs, 24.2 ± 0.4 kg/m2) were studied. MSNA was measured via peroneal microneurography and blood pressure was measured with a brachial intraarterial catheter. Women and men had similar mean arterial pressures (91 ± 1 vs. 90 ± 1 mmHg), cardiac BRS (19 ± 1 vs. 21 ± 2 ms/mmHg), and sympathetic BRS (−6 ± 0.4 vs. −7 ± 0.6 AU/beat/mmHg), respectively. The decrease in systolic blood pressure (SBP) and pulse pressure (PP) was positively related to cardiac BRS in men (r=.47; p&lt;0.01; r=.49; p&lt;0.01). However, there was no relationship between the decrease in blood pressure and sympathetic BRS in men. In addition, there was no association between any blood pressure transients with either cardiac or sympathetic BRS in women. Our results suggest the magnitude of decrease in blood pressure is associated with cardiac BRS in men, but not women.Funded by NIH

Nafamostat Mesilate Attenuates Postreperfusion Syndrome during Liver Transplantation

Postreperfusion syndrome (PRS), an acute decrease in blood pressure after reperfusion of the liver graft, occurs frequently during liver transplantation surgery. We supposed that the activation of the kallikrein-kinin system leading to extensive systemic vasodilatation was a possible cause. The effect of pretreatment with nafamostat mesilate (NM), a broad spectrum serine protease inhibitor, on the occurrence of PRS was evaluated. Sixty-two adult liver recipients were randomized to receive an intravenous bolus of either 0.02 mg/kg of NM (NM group, n = 31) or an equal volume of normal saline (control group, n = 31) just before reperfusion of the liver graft. Occurrence of PRS and intraoperative use of vasoactive drugs were compared between the two groups. Postoperative recovery was also compared. PRS was significantly less frequent (48% vs. 81%, p = 0.016) requiring less vasopressors in the NM group compared to the control group. The NM group also showed faster recovery of the mean arterial pressure. Perioperative laboratory values were similar between the two groups. Pretreatment with 0.02 mg/kg of NM immediately before reperfusion decreases the frequency of PRS and vasopressor requirements during the reperfusion period in liver transplantation.

Does nicotinic acid (niacin) lower blood pressure?

Nicotinic acid (niacin) is a well-established treatment for dyslipidaemia – an important cardiovascular disease (CVD) risk factor. However, niacin may also reduce blood pressure (BP), which is another important CVD risk factor. This review examines the limited publicly available data on niacin’s BP effects. Acute administration of immediate-release niacin may lower BP because of niacin’s acute vasodilatory effects. Although not always supported by clinical trial data, the package insert of a prescription, extended-release niacin describes niacin-induced acute hypotension. From a chronic standpoint, larger studies, such as the Coronary Drug Project, suggest that niacin may lower BP when administered over a longer period of time. Post hoc analyses of some of the more recent niacin clinical trials also support a more chronic, dose-dependent, BP-lowering effect of niacin. Because laropiprant [a prostaglandin D2 (PGD2) type 1 (DP1) receptor antagonist] does not attenuate niacin’s BP-lowering effects, it is unlikely that any chronic lowering of BP by niacin is due to dilation of dermal vessels through activation of the DP1 receptor by PGD2. Further research is warranted to evaluate the extent and mechanisms of niacin’s effects on BP.

Effects of Autogenic Training on Nitroglycerin‐Induced Headaches

Objectives.—To investigate the prophylactic and acute effects of autogenic training (AT) during a nitroglycerin‐induced migraine attack.Methods.—Thirty female migraineurs (without aura) and 11 controls participated in the study. Of these, 11 migraineurs and 5 controls practiced AT regularly for at least 6 months prior to and during the sublingual nitroglycerin test. Headache intensity and characteristics were recorded with a standardized method. During the nitroglycerin challenge, blood was collected for plasma cortisol determination and blood pressure and pulse rate were recorded.Results.—As a long‐term preventive treatment, AT significantly decreased the mean headache frequency and intensity (P= .001) compared to the pretreatment period in the migraineurs who regularly practiced AT (n = 11). During the nitroglycerin challenge, AT successfully attenuated the nitroglycerin‐induced acute decrease in blood pressure and pulse rate (P= .013; n = 16 AT subjects vs n = 25 non‐AT subjects). However, it was not effective in preventing immediate headache (P= .71), did not decrease the frequency of acute migraine attacks (P= .79), and could not alleviate acute migraine pain (P= .78; n = 16 AT subjects vs n = 25 non‐AT subjects). Plasma cortisol concentration significantly increased (P= .003) during the acute migraine attack (n = 22), and migraine intensity correlated with plasma cortisol elevations (P &lt; .001; n = 41) and showed a tendency of negative correlation with morning plasma cortisol concentration (P= .08; n = 41). However, AT did not alter plasma cortisol responses (P= .99; n = 16 AT subjects vs n = 25 non‐AT subjects).Conclusion.—(1) The long‐term AT therapy proved to be a significantly effective preventive intervention in migraine sufferers. We hypothesized that this long‐term effect of AT is based on modulation of the pain anticipation system, which is strongly correlated with function of the anterior cingulate cortex. (2) We demonstrated that AT could not alter the nitroglycerin‐induced acute migraine attacks, which are directly related to the dysfunctional brainstem activation according to previous studies. (3) Our results suggested that there are multiple, complex relationships between cortisol responses and migraine pain, which are possibly mediated by the brain serotonergic system. (4) In addition, our results provide further evidence that nitroglycerin‐induced vasodilatation is not directly connected to either immediate headache or delayed migraine attack.

An implantable carotid sinus stimulator for drug-resistant hypertension: Surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial

A large number of patients have hypertension that is resistant to currently available pharmacologic therapy. Electrical stimulation of the carotid sinus baroreflex system has been shown to produce significant chronic blood pressure decreases in animals. The phase II Rheos Feasibility Trial was performed to assess the response of patients with multidrug-resistant hypertension to such stimulation. The system consists of an implantable pulse generator with bilateral perivascular carotid sinus leads. Implantation is performed bilaterally with patients under narcotic anesthesia (to preserve the reflex for assessment of optimal lead placement). Dose-response testing at 0 to 6 V is assessed before discharge and at monthly intervals thereafter; the device is activated after 1 month's recovery time. This was a Food and Drug Administration-monitored phase II trial performed at five centers in the United States. Ten patients with resistant hypertension (taking a median of six antihypertensive medications) underwent implantation. All 10 were successful, with no significant morbidity. The mean procedure time was 198 minutes. There were no adverse events attributable to the device. Predischarge dose-response testing revealed consistent (r = .88) reductions in systolic blood pressure of 41 mm Hg (mean fall is from 180-139 mm Hg), with a peak response at 4.8 V (P < .001) and without significant bradycardia or bothersome symptoms. A surgically implantable device for electrical stimulation of the carotid baroreflex system can be placed safely and produces a significant acute decrease in blood pressure without significant side effects.

Postoperative Thrombotic Microangiopathy following Radical Cystectomy for Bladder Cancer

This report describes the perioperative management of disseminated intravascular coagulation occurring abruptly during a planned cystectomy for non-metastatic bladder papillary carcinoma. Peroperatively, profuse bleeding and an acute decrease in blood pressure were effectively treated by blood transfusions and fresh frozen plasma. Haematological tests indicated the presence of disseminated intravascular coagulation. On the following three days, acute renal failure, peripheral disseminated intravascular coagulation-related thrombocytopenia and haemolytic anemia with schistocytes were suggestive of thrombotic microangiopathy. Treatment by plasma exchange along with haemodialysis was commenced. An aetiological work-up remained negative. After 21 days of treatment, haemodialysis and plasma exchange were stopped. Urological outcome was favourable. The one-year follow-up did not show any residual renal insufficiency and laboratory parameters returned to normal. In the absence of evidence in favour of an infectious, drug-related or immunological aetiology, we postulated that this thrombotic microangiopathy was caused by disseminated intravascular coagulation and that the tumour manipulation during the surgical procedure was the triggering factor.

Paradoxical changes in brain natriuretic peptide levels and loading conditions after intravenous conscious sedation

Background Elevated filling pressure and wall stress have been proposed as stimuli for elevated brain natriuretic peptide (BNP) levels. Narcotic and benzodiazepine sedation, such as is used for transesophageal echocardiography (TEE), is known to decrease filling pressures. We hypothesized that lower filling pressure and wall stress associated with intravenous conscious sedation (IVCS) would lead to lower BNP levels. Methods We studied BNP levels, blood pressure, and echocardiographic indices of filling pressure and wall stress before and after IVCS and TEE. Results When data before and after IVCS and TEE were compared, mean blood pressure decreased (149 ± 24/83 ± 14 mm Hg vs 126 ± 29/69 ± 14; P < .01), as did mitral Doppler E wave velocity (82 ± 23 cm/s vs 76 ± 22; P < .05), right ventricular/atrial gradient (31 ± 10 mm Hg vs 29 ± 13; P < .05), and wall stress. However, BNP levels increased (195 ± 407 pg/mL vs 238 ± 458; P < .01). Conclusions In a series of patients undergoing clinically indicated TEE, BNP levels increase above baseline after IVCS. The increase in BNP occurs despite lower blood pressure, lower mitral Doppler E velocity, lower right ventricular/atrial gradient, and lower wall stress compared with baseline. The mechanism of the paradoxical increase in BNP is not entirely clear, but it may conceivably be a result of counterregulatory hormone release caused by acute decrease in blood pressure.

Dynamics of cerebral blood flow autoregulation in hypertensive patients

In hypertensive patients, the upper and lower limits of cerebral autoregulation are shifted to higher levels. However, the dynamics of cerebral autoregulation in hypertensive patients are less well known. We compared the dynamics of cerebral autoregulation in 21 treated hypertensive patients (13 men and 8 women; mean age: 48.9±13.6 years) and in 21 normotensive subjects (13 men and 8 women; mean age: 51±14.5 years) by transcranial Doppler (TCD) of the middle cerebral artery (MCA) during the acute decrease in blood pressure induced by standing up after 2 min in squatting position. MCA maximal outline blood flow velocity (FV), blood pressure (Finapres) and end-tidal PCO 2 were continuously monitored and computerised. A cerebral vascular resistance index (CR) was calculated as follows: mean arterial BP/MCA mean FV with normalised changes in CR per second during the blood pressure decrease (CR slope). The CR slope reflecting the rate of cerebral autoregulation did not differ between the two groups and within the hypertensive patients [well controlled (8 patients) and not controlled (13 patients)]. The time to maximum decrease of CR ( T 1) and the time to full recovery of CR after the initial drop ( T 2) were also similar in the two groups (controls T 1: 11.3±3.1 s, T 2: 12±5.9 s; hypertensive T 1: 11.7±2.5 s, T 2: 10.7±4.5 s) and within hypertensive patients. These findings suggest that the dynamics of cerebral autoregulation are well preserved in hypertensive patients, with no difference according to the efficiency of treatment of hypertension.

Renal denervation altered the hemodynamic and renal effects following intracerebroventricular administration of the I 1-imidazoline receptor agonist, rilmenidine, in pentobarbital anaesthetized rats

Previous studies have reported on the effects of intracerebroventricular (icv) administration of the I 1-imidazoline receptor agonist moxonidine. In the present study, the relationship between increasing doses of the I 1-agonist rilmenidine (administered icv) with blood pressure and renal function has been determined. Moreover, the importance of the renal nerves in this response have also been assessed. In pentobarbitone anesthetized rats, icv rilmenidine (30, 100, 300 nmol in 5μl) produced a dose related decrease in blood pressure and heart rate. Urine flow was not altered at the lower doses although at the highest dose (300 nmol) the increase approached significance ( p = 0.06). Sodium excretion and osmolar clearance were not altered. Free water clearance was increased at 100 and 300 nmol rilmenidine ( p < 0.05). Consistent with the above dose response studies, in sham denervated rats icv rilmenidine (300 nmol) decreased blood pressure and increased free water clearance. In rats having undergone renal denervation, baseline levels of urine flow rate, sodium excretion and osmolar clearance were increased. In these denervated r rats, icv rilmenidine (300 nmol) failed to decrease blood pressure. Urine flow rate was increased with a decrease in sodium excretion and osmolar clearance. Free water clearance was increased. These results indicate the importance of the renal nerves in mediating the acute decrease in blood pressure following icv administration of the I 1-imidazoline receptor agonist rilmenidine. The increase in free water clearance seen following icv rilmenidine appears to be mediated independent of the renal nerves. The changes associated with sodium excretion on the contrary are dependent on intact renal nerves.

The use of moxonidine in the treatment of hypertension.

Imidazoline I1-receptor agonism represents a new mode of antihypertensive action to inhibit peripheral alpha-adrenergic tone by a central mechanism. Adrenaline, noradrenaline and renin levels are reduced, a finding consistent with central inhibition of sympathetic tone. Acute haemodynamic studies indicate that moxonidine results in an acute decrease in blood pressure due to a fall in systemic vascular resistance, whereas the heart rate, cardiac output, stroke volume and pulmonary artery pressures are not affected. Left ventricular end systolic and diastolic volumes are reduced. Left ventricular hypertrophy has been found to regress after 6 months of treatment. Following oral administration, maximum concentration is reached at about 1 h, and bioavailability approaches 90%. Moxonidine is mostly excreted unchanged, and biotransformation is unimportant. The half-life of moxonidine is 2.5 h, which is prolonged by renal insufficiency. However, the antihypertensive effect lasts longer than would be expected from the half-life, suggesting possible retention in the central nervous system. Decreases of about 20-30 mmHg systolic and 10-20 mmHg diastolic blood pressure have been found in open studies with moxonidine. The dosage of 0.2-0.4 mg moxonidine daily controls hypertension in most patients. Moxonidine has been compared with representatives from each important class of antihypertensive drugs, with clonidine, diuretics, both alpha- and beta-blocking drugs, calcium antagonists and angiotensin converting enzyme inhibitors. Blood pressure control has been observed to be similar with moxonidine and these other agents. Generally, the overall incidence of side-effects has been found to be similar, although the incidence of side-effects with clonidine is greater than that seen with moxonidine. A meta-analysis of controlled studies with moxonidine found that moxonidine gave similar reductions in blood pressure in both men and women, in those aged below 50, 50-60 and over 60 years, and regardless of body weight. As often seen with some other drugs, higher systolic blood pressures are associated with larger reductions in systolic blood pressure and the same appears to be the case with diastolic blood pressure.

A pharmacokinetically based propofol dosing strategy for sedation of the critically ill, mechanically ventilated pediatric patient.

To assess the pharmacokinetics and pharmacodynamics of propofol sedation of critically ill, mechanically ventilated infants and children. A prospective clinical study. A pediatric intensive care unit (ICU) in a university hospital. Clinically stable, mechanically ventilated pediatric patients were enrolled into our study after residual sedative effects from previous sedative therapy dissipated and the need for continued sedation therapy was defined. Patients were generally enrolled just before extubation. A stepwise propofol dose escalation scheme was used to determine the steady-state propofol dose necessary to achieve optimal sedation, as defined by the COMFORT scale, a validated scoring system which reliably and reproducibly quantifies a pediatric patient's level of distress. When in need of continued sedation, study patients received an initial propofol loading dose of 2.5 mg/kg and were immediately started on a continuous propofol infusion of 2.5 mg/kg/hr. The propofol infusion rate was adjusted and repeat loading doses were administered, if needed, using a coordinated dosing scheme to maintain optimal sedation for a 4-hr steady-state period. After 4 hrs of optimal sedation, the propofol infusion was discontinued and simultaneous blood sampling and COMFORT scores were obtained until the patient recovered. Additional blood samples were obtained up to 24 hrs after stopping the infusion and analyzed for propofol concentration by high-performance liquid chromatography. Twenty-nine patients were enrolled into this study. One patient was withdrawn from this study because of an acute decrease in blood pressure occurring with the first propofol loading dose; 28 patients completed the study. All patients were sedated immediately after the first 2.5-mg/kg propofol loading dose. Eight patients were adequately sedated with the starting propofol dose regimen, whereas five patients required downward dose adjustment and 11 patients required dosage increases to achieve optimal sedation. Four patients failed to achieve adequate sedation after five dose escalations and the drug was stopped. Recovery from sedation (COMFORT score of > or = 27) after stopping the propofol infusion was rapid, averaging 15.5 mins in 23 of 24 evaluable patients. In 13 patients who were extubated after stopping the propofol infusion, the time to extubation was also rapid, averaging 44.5 mins. Determination of the blood propofol concentration at the time of recovery from propofol sedation was possible in 15 patients. The blood propofol concentration was variable, ranging between 0.262 to 2.638 mg/L but < or = 1 mg/L in 13 of 15 patients. Similarly, tremendous variation was observed in propofol pharmacokinetics. Propofol disposition was best characterized by a three-compartment model with initial rapid distribution into a small central compartment, V1, and two larger compartments, V2 and V3, which are two-and 20-fold greater in volume, respectively, than V1. Redistribution from V2 and V3 into V1 was much slower than ingress, underscoring the importance of the propofol concentration in V1 as reflective of the drug's sedative effect. Propofol was well tolerated. Two patients experienced an acute decrease in blood pressure which resolved without treatment. We conclude that a descending propofol dosing strategy, which maintains the propofol concentration constant in the central compartment (V1) while drug accumulates in V2 and V3 to intercompartmental steady-state, is necessary for effective propofol sedation in the pediatric ICU. Our proposed dosing scheme to achieve and maintain the blood propofol concentration of 1 mg/L would appear effective for sedation of most clinically stable, mechanically ventilated pediatric patients.

Hemodynamics of respiratory failure in rabbit model: effect of surfactant supplementation.

In some infants, administration of surfactant has been associated with an acute decrease in blood pressure. We hypothesized that independent of patent ductus arteriosus, low blood volume sensitizes to a negative hemodynamic response to surfactant supplementation. Respiratory failure was induced by bronchoalveolar lavage (BAL) in 30 young rabbits that were paralyzed and ventilated using tidal volumes of 10 ml/kg. After BAL, 15 ml/kg blood was withdrawn while the same volume of one of the following was infused: Ringer's lactate (n = 12); 5% albumin (n = 5); or leukocyte-free red blood cells (RBC, n = 6). The controls were not phlebotomized (n = 7). After blood withdrawal and transfusion, natural surfactant was given (100 mg/kg). The blood volume and pulmonary capillary leak were calculated. Cardiac output (CO) and vascular resistances were measured (Ringer's lactate; n = 5; controls, n = 4). Blood withdrawal and replacement had no immediate effect on either lung function or hemodynamics. Surfactant supplementation improved the gas exchange in all but the albumin-treated animals that had increased protein concentration in epithelial lining fluid. In the Ringer's lactate group, there was a 35% decrease (p < 0.05) in blood pressure, a 28% decrease (p < 0.05) in CO, and a 54% increase (p < 0.05) in pulmonary vascular resistance, shortly after surfactant administration. In the other groups, there was either a transient (controls) or no (RBC and albumin groups) decrease in blood pressure. The total blood volume and the intrapulmonary blood volume were lower in the Ringer's lactate group than in the RBC group. According to the present results, blood pressure and CO may decrease acutely when exogenous surfactant is administered coincidental with blood loss.

Effects of propofol and fentanyl on the baroreceptor reflex in geriatric patients

Increasing age and anaesthetics diminish the baroreflex response to acute changes in blood pressure. This study was designed to investigate the effects of propofol and the combination of propofol with fentanyl on the baroreflex activity in geriatric patients. Baroreflex sensitivity was studied by the method of Smyth et al. in 10 elderly (72 +/- 6 yrs) and in 10 younger (48 +/- 6 yrs) patients. Nitroprusside (depressor test) and phenylephrine (pressor test) were used to induce changes in blood pressure of 20 mmHg each to alter the stimulation of the baroreceptor sites. Anaesthesia was induced with propofol, 2 mg x kg-1 b.w.m, and maintained by a continuous infusion of 12 mg x kg-1 x h-1 for 10 min and thereafter with 6 mg x kg-1 x h-1. Then a bolus of fentanyl, 7 micrograms x kg-1 b.w. was injected. Haemodynamic parameters and baroreflex activity were measured in the awake state, 10 min after induction of anaesthesia and 10 min after the administration of fentanyl. Plasma propofol concentrations were determined by HPLC 10 min after induction of anaesthesia with propofol and 10 min after injection of fentanyl. The slope of the linear regression changes in RR-interval [ms] per changes in systolic pressure [mmHg] was used as an index of the baroreflex sensitivity. In the awake state the depressor slopes were significantly reduced by 60% in the elderly patients when compared to the younger patients. In both groups propofol decreased reflex sensitivity by 38% and 41% respectively; this effect was enhanced by the addition of fentanyl in the younger patients, while there was no further effect in the elderly. The pressor slopes did not change significantly in both groups neither with propofol nor with the combination of fentanyl, but again reflex response was significantly less in the elderly patients. Our data demonstrate that in geriatric patients the baroreflex control of heart rate already is attenuated in the awake state. Propofol produces a further reduction in reflex sensitivity to an acute decrease in blood pressure; this effect is more pronounced in elderly patients as compared to younger individuals. Acute changes in posture or circulating blood volume during propofol anaesthesia may result in greater cardiovascular instability in older patients due to the greater impairment of circulatory control mechanisms.

Large dose of flunitrazepam attenuates baroreflex control of heart rate in man.

The effects of intravenous tranquilizers such as flunitrazepan, diazepam and droperidol on baroreflex control of heart rate were investigated using both pressor and depressor tests. The dose-dependency was also studied by the administration of the drugs at the usual or twofold dosage. The usual dosage caused no significant change in neuronal controlling mechanism of circulation. However, flunitrazepam at double the usual dosage produced a decrease in baroreflex sensitivity at depressor tests. The results suggest that flunitrazepam when given repeatedly might accelerate hemodynamic derangements induced by an acute decrease in blood pressure.

A comparison of the acute effects of cicletanine and bendrofluazide on urinary electrolytes and plasma potassium in essential hypertension

The acute effects on urinary electrolyte excretion and plasma potassium were compared of the anti-hypertensive dihydrofuropyridine cicletanine with the thiazide bendrofluazide in 6 patients with uncomplicated essential hypertension. Cicletanine 50 mg or 100 mg and bendrofluazide 5 mg caused no acute decrease in blood pressure compared to placebo for 24 h after treatment. In the 24 h after a single dose of cicletanine 50 mg there was no increase in urinary sodium, potassium or volume compared to placebo. After a single dose of cicletanine 100 mg there was a significant increase in 2 h urinary sodium excretion compared to cicletanine 50 mg and in the first 6 h a significant increase in urinary potassium compared to placebo. Urine volume did not change significantly. After bendrofluazide 5 mg urinary sodium excretion increased significantly in the first 6 h as well as in the subsequent 18 h compared to placebo and both cicletanine 50 mg and 100 mg. Urinary potassium excretion was also significantly increased in the first 6 h after bendrofluazide compared to placebo, and urine volume significantly increased from 6 to 24 h after bendrofluazide 5 mg compared to placebo and cicletanine 100 mg. Plasma potassium was significantly reduced and plasma renin activity significantly increased 24 h after bendrofluazide 5 mg but these measurements were not significantly different from placebo after cicletanine 50 or 100 mg. These results suggest that cicletanine 100 mg has milder acute natriuretic effects than the thiazide bendrofluazide 5 mg. In contrast cicletanine 50 mg is associated with no major acute renal effects.(ABSTRACT TRUNCATED AT 250 WORDS)