Mean Arterial Blood Pressure Measurements Research Articles

Transient growth hormone therapy to rats with low protein-inflicted intrauterine growth restriction does not prevent elevated blood pressure in later life

Intrauterine growth restriction (IUGR) is a risk factor for the development of hypertension in later life. Insulin-like growth factor I and growth hormone (GH) have the potential to improve metabolic syndrome after IUGR in adult animals. The objective of the present study was to examine whether transient GH treatment of pups after weaning can prevent the development of arterial hypertension in adult rats.IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams and litter size was reduced to six male neonates after birth. Recombinant human GH was applied by daily subcutaneous injections at a dose of 3 μg/g body weight between days 24 and 60 of life. Control animals received vehicle treatment (VEH) only.Birth weight was significantly lower in low protein (LP) animals than in normal protein (NP) animals (5.1 ± 0.3 g vs. 5.9 ± 0.7 g, p < 0.05). Until weaning at day 23, LP animals reached similar body length, but had reduced body weight compared to NP animals. Intraarterially measured mean arterial blood pressure at day 120 was elevated in LP-VEH compared to NP-VEH animals (113 ± 6 mmHg vs. 101 ± 6 mmHg, p < 0.01). However, transient GH-treatment did not prevent arterial hypertension in LP animals (112 ± 5 mmHg).Our data suggest that GH treatment between days 24 and 60 of life does not or at least not permanently reprogram blood pressure elevation after IUGR.

Regulator of G protein signalling 2 ameliorates angiotensin II‐induced hypertension in mice

Angiotensin II (Ang II) activates signalling pathways predominantly through the G-protein-coupled Ang II type 1 receptor (AT(1)R). The regulator of G protein signalling 2 (RGS2) is a negative G protein regulator. We hypothesized that RGS2 deletion changes blood pressure regulation by increasing the response to Ang II. To address this issue, we infused Ang II (0.5 mg kg(-1) day(-1)) chronically into conscious RGS2-deleted (RGS2(-/-)) and wild-type (RGS2(+/+)) mice, measured mean arterial blood pressure and heart rate (HR) with telemetry and assessed vasoreactivity and gene expression of AT(1A), AT(1B) and AT(2) receptors. Angiotensin II infusion increased blood pressure more in RGS2(-/-) than in RGS2(+/+) mice, while HR was not different between the groups, indicating a resetting of the baroreceptor reflex. Urinary catecholamine excretion was similar in Ang II-infused RGS2(-/-) and RGS2(+/+) mice, indicating a minor role of sympathetic tone for blood pressure differences. Myogenic tone and vasoreactivity in response to Ang II, endothelin-1 and phenylephrine were increased in isolated renal interlobar arterioles of RGS2(-/-) mice compared with RGS2(+/+) mice. The AT(1A), AT(1B) and AT(2) receptor gene expression was not different between RGS2(-/-) and RGS2(+/+) mice. Our findings suggest that RGS2 deletion promotes Ang II-dependent hypertension primarily through an increase of myogenic tone and vasoreactivity, probably by sensitization of AT(1) receptors.

Effect of prone position without PEEP on oxygenation and complacency in an experimental model of lung injury

To observe the effects of the prone position and the need for positive end-expiratory pressure (PEEP) to improve oxygenation.Sixteen rats were anesthetized and ventilated at a tidal volume of 8 mL/kg, respiratory rate of 60 rpm and PEEP = 0 cmH(2)O (ZEEP), in the supine position for 30 minutes. Lung injury was then induced by means of intratracheal instillation of hydrochloric acid. Once the injury was established, rats were placed in the prone position for a further 30 minutes and randomized into two groups: in group 1 PEEP = 5 cmH(2)O was added; while group 2 was kept on ZEEP. Measurements of pulmonary mechanics, arterial blood gas analysis and mean arterial pressure were taken at the end of each phase.In group 1, oxygen partial pressure increased significantly from 98.7+/-26.5 to 173.9+/-58.4 mmHg between injury and prone phases; in group 2 it was unchanged, varying from 99.6+/-15.4 to 100.5+/-24.5 mmHg. Group 1 also exhibited significant improvement in complacency, from 0.20+/-0.01 to 0.23+/-0.02 mL/cmH(2)O, while, once more, group 2 did not exhibit improvement, going from 0.21+/-0.02 to 0.22+/-0.01 mL/cmH(2)O. Mean arterial blood pressure measurements did not change significantly in either group at any point during the experiment.The prone position only resulted in improved oxygenation and respiratory mechanics when combined with PEEP = 5 cmH(2)O. The prone position did not cause hemodynamic compromise with or without PEEP = 5 cmH(2)O.

Modulation of the spontaneous beat-to-beat fluctuations in peripheral vascular resistance during activation of muscle metaboreflex

Continuous measurement of leg blood flow (LBF) using Doppler ultrasound with simultaneous noninvasive mean arterial blood pressure (MAP) measurement permits beat-to-beat estimates of leg vascular resistance (LVR) in humans. We tested the hypothesis that the beat-to-beat fluctuations in LVR and the dynamic relationship between MAP and LVR are modulated by the activation of muscle metaboreflex. Twelve healthy subjects performed a 1-min isometric handgrip exercise at 50% maximal voluntary contraction, which was followed by a period of imposed postexercise muscle ischemia (PEMI). We then employed transfer function analysis to examine the dynamic relationships between MAP and LBF and between MAP and LVR, both at rest (control) and during PEMI. We found the following. 1) The spectral power for LBF and LVR in low-frequency ( approximately 0.03-0.15 Hz) range significantly increased from control during PEMI without a significant change in the high-frequency ( approximately 0.15-0.35 Hz) power. 2) During PEMI, the transfer function gains for MAP-LBF and MAP-LVR relationships in the low-frequency ( approximately 0.05-0.15 Hz) range were significantly increased during PEMI (vs. control) but were unchanged in the high-frequency ( approximately 0.2-0.3 Hz) range. 3) The phases for MAP-LBF and MAP-LVR relationships were not different during control and PEMI. The phase for MAP-LVR relationship revealed that changes in MAP were followed by directionally similar changes in LVR, which is consistent with the characteristics of intrinsic vascular regulatory mechanisms such as the myogenic response of the resistance arteries. We suggest that, in humans, modulation of the dynamic MAP-LVR relationship during activation of the muscle metaboreflex reflects complex interactions between intrinsic vascular regulatory mechanisms and sympathetic vascular regulation.

Assessment of blood pressure in cats presented with urethral obstruction

AbstractObjective: To determine the arterial blood pressure at presentation in male cats with acute urethral obstruction, and to determine whether there was any correlation between these measurements and concurrent metabolic abnormalities.Design: Prospective, single cohort, observational study.Setting: Private, small animal, after‐hours emergency clinic.Animals: Twenty‐eight client‐owned male cats with acute urethral obstruction and no other known coexisting disease.Interventions: Indirect oscillometric blood pressure measurements obtained before blood sampling and treatment.Measurements and main results: Mean arterial blood pressure (MAP) measurements, physical examination parameters, serum blood urea nitrogen (BUN), creatinine, potassium, phosphorus, total calcium and magnesium concentration, venous pH, lead II electrocardiogram, and urine volume in bladder were evaluated. No cats were hypotensive at presentation; 71% (20/28) were normotensive (median MAP=100 mmHg, range 93–140 mmHg); and 29% (8/28) were hypertensive (median MAP=153 mmHg, range 145–176 mmHg). Compared with hypertensive cats, normotensive cats had significantly lower heart rates (P=0.0201) and lower calcium (P=0.0152). For all 28 cats, MAP correlated with serum potassium and total calcium (P=0.0033).Conclusions: Though potassium and total calcium were inversely and directly correlated respectively with blood pressure in cats with urethral obstruction, none of the cats were hypotensive on presentation. Normotension on admission does not support the absence of biochemical and physical abnormalities in obstructed cats.

Fiabilité et survie du cathéter artériel : réponse dynamique optimale

Objectives Blood pressure is one of the most critical haemodynamic parameter in the intensive care unit (ICU). The measurement relies mainly on invasive methods (arterial lines) but also on noninvasive methods (Oscillometric and Manual). It is crucial to be instantaneous and accurate to adapt any decision making plan. The aim of this study is to evaluate the reliability of this measure given by an arterial catheter over time. This can determine the maintenance of catheter patency before clinical total occlusion. Study design Observational prospective study. Patients and methods Damping coefficient (ξ) and natural frequency (Fn) of the arterial catheter system are studied in vivo each 12 hours by a fast flush test (FFT) in 61 patients. The measurements of the arterial blood pressure invasively (arterial catheter method) and non invasively (oscillometric method) are compared each 12 hours until the catheter is removed. Results All over the study period for each catheter (till 240 hours), the mean arterial blood pressure measurements given by either the catheter method or the oscillometric method were very concordant (coefficient > 0.7). Only 3.39% of the catheters had their physical characteristics (ξ and Fn) in the optimal zone at T0; reaching 66.67% at T19. The maximal inserted time was highly correlated with a good operating catheter ( R = 0.739; P < 10 –4). Conclusion The measure of the arterial blood pressure invasively can still be reliable for a long period of time (10 days), as long as the catheter is inserted, especially when the mean arterial pressure is considered. Each time the distance of the catheter insertion site moves away 1 cm from the radiocarpal joint or the groin, the risk of troubleshooting is doubled; on each blood sample from the catheter, this risk is reduced by 20%.

Arterial Pulse Pressure and Its Association With Reduced Stroke Volume During Progressive Central Hypovolemia

The reduction of stroke volume (SV) during hemorrhage reflects the degree of blood loss, but accurate assessment of SV in bleeding patients in the field currently is not possible. In a previous pilot study, we reported that arterial pulse pressure and estimated sympathetic nerve activity (SNA) in trauma patients who died of hemorrhagic injuries was significantly lower than that observed in patients who did not die. For the current study, we measured mean arterial blood pressure (MAP), pulse pressure (PP), SV, and muscle sympathetic nerve activity (MSNA) in human subjects during progressive lower body negative pressure (LBNP) to test the hypothesis that a reduction in PP tracks the reduction of SV and change in MSNA during graded central hypovolemia in humans. After a 12-minute baseline data collection period, 13 men were exposed to LBNP at -15 mm Hg for 12 minutes followed by continuous stepwise increments to -30, -45, and -60 mm Hg for 12 minutes each. Comparing baseline to -60 mm Hg chamber decompression, systolic blood pressure (SBP) decreased (from 129 +/- 3.0 to 111 +/- 6.1 mm Hg; p = 0.005) and diastolic pressure was unchanged (78 +/- 3.0 versus 81 +/- 4.0 mm Hg; p = 0.55). Pulse pressure decreased (from 50 +/- 2.5 to 29 +/- 4.0 mm Hg; p = 0.0001). LBNP caused linear reductions in PP and SV (from 125 +/- 9.2 to 47 +/- 6.4; r2 = 0.99), and increases in MSNA (from 14 +/- 3.5 to 36 +/- 4.6 bursts/min; r2 = 0.96) without a significant change in MAP (r2 = 0.28). PP was inversely correlated with MSNA (r2 = 0.88) and positively correlated with SV (r2 = 0.91). Reduced PP resulting from progressive central hypovolemia is a marker of reductions in SV and elevations in SNA. Therefore, when SBP is >90 mm Hg, PP may allow for early, noninvasive identification of volume loss because of hemorrhage and more accurate and timely triage.

Altered nitric oxide mechanism within the paraventricular nucleus contributes to the augmented carotid body chemoreflex in heart failure

Our previous study demonstrated a contribution of the paraventricular nucleus (PVN) of the hypothalamus in the processing of the carotid body (CB) chemoreflex. Nitric oxide (NO) (within the PVN), known to modulate autonomic function, is altered in rats with heart failure (HF). Therefore, the goal of the present study was to examine the influence of endogenous and exogenous NO within the PVN on the sympathoexcitatory component of the peripheral chemoreflex in normal and HF states. We measured mean arterial blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) in sham-operated and HF rats (6-8 wk after coronary artery ligation) after incremental doses of potassium cyanide (25-100 mug/kg iv). There was potentiation of the reflex responses in HF compared with sham-operated rats. Bilateral microinjection of an inhibitor of NO synthase, N(G)-monomethyl-l-arginine (50 pmol), into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation in sham-operated rats but had no effect in HF rats. Conversely, bilateral microinjection of a NO donor, sodium nitroprusside (50 nmol), into the PVN attenuated the RSNA response of the peripheral chemoreflex in sham-operated rats but to a smaller extent in HF rats. These data indicate that 1) NO within the PVN plays an important role in the processing of the CB chemoreflex and 2) there is an impairment of the NO function within the PVN of HF rats, which contributes to an augmented peripheral chemoreflex and subsequent elevation of sympathetic activity in HF.

Androgens augment renal vascular responses to ANG II in New Zealand genetically hypertensive rats

Males develop higher blood pressure than do females. This study tested the hypothesis that androgens enhance responsiveness to ANG II during the development of hypertension in New Zealand genetically hypertensive (NZGH) rats. Male NZGH rats were obtained at 5 wk of age and subjected to sham operation (Sham) or castration (Cas) then studied at three age groups: 6-7, 11-12, and 16-17 wk. Mean arterial blood pressure (MAP), heart rate (HR), and renal blood flow (RBF) measurements were recorded under Inactin anesthesia. These variables were measured after enalapril (1 mg/kg) treatment and during intravenous ANG II infusion (20, 40, and 80 ng/kg/min). Plasma testosterone was measured by ELISA. Angiotensin type 1 (AT1) receptor expression was assessed by Western blot analysis and RT-PCR. ANG II-induced MAP responses were significantly attenuated in Cas NZGH rats. At the highest ANG II dose, MAP increased by 40+/-4% in Sham vs. 22+/-1% in Cas NZGH rats of 16-17 wk of age. Similarly, renal vascular resistance (RVR) responses to ANG II were reduced by castration (209+/-20% in Sham vs. 168+/-10% in Cas NZGH rats at 16-17 wk of age). Castration also reduced MAP recorded in conscious NZGH rats of this age group. Testosterone replacement restored baseline MAP and the pressor and RVR responses to ANG II. Castration reduced testosterone concentrations markedly. Testosterone treatment restored these concentrations. Neither castration nor castration+testosterone treatment affected AT1 receptor mRNA or protein expression. Collectively, these data suggest that androgens modulate renal and systemic vascular responsiveness to ANG II, which may contribute to androgen-induced facilitation of NZGH rat hypertension.

Effect of 5-lipoxygenase blockade on blood pressure and acetylcholine-evoked endothelium-dependent contraction in aorta from spontaneously hypertensive rats

Cysteinyl leukotrienes (cysLT) are pro-inflammatory and vasoactive products suspected to be involved in the regulation of vascular tone and blood pressure in hypertension. We investigated, in spontaneously hypertensive rats (SHR), the involvement of cysLT in the in-vivo regulation of blood pressure and the in-vitro endothelium-dependent contraction to acetylcholine in isolated aorta. SHR and Wistar-Kyoto rats (WKY) were orally treated for 3 weeks with either the cysLT biosynthesis inhibitor MK-886 (0.1 mg/ml) or vehicle. After mean arterial blood pressure (MABP) measurement, aortic ring preparations were removed from all groups of animals, and contractions and relaxations were monitored subsequent to stimulation with acetylcholine. MABP was higher in SHR. Chronic treatment with MK-886 did not alter MABP in either SHR or WKY. In the presence of the N-nitro-L-arginine (L-NA, 100 micromol/l), and on prostaglandin F2alpha (PGF2alpha)-induced tone, acetylcholine evoked concentration-dependent contractions in intact aortic rings from SHR only. Pretreatment with either MK-886 (10 micromol/l), the 5-lipoxygenase (5-LO) inhibitor AA861 (10 micromol/l), or the cysLT1 receptor antagonist MK571 (1 micromol/l) reduced (P < 0.05) acetylcholine-induced contractions in intact aortic rings from SHR only. Acetylcholine-induced contractions were weaker (P < 0.01) in SHR chronically treated with MK-886 than in SHR. In the presence of L-NA, leukotriene (LT) D4 induced greater (P < 0.05) concentration-dependent contractions in aortic rings from SHR than from WKY. MK571 abolished LTD4-evoked contractions. These data suggested that 5-LO-derived products, through the activation of cysLT1 receptors, could be involved in the endothelium-dependent contraction to acetylcholine in aorta from SHR but not in the regulation of MABP in SHR.

NO-dependent blood pressure regulation in RGS2-deficient mice

The regulator of G protein signaling (RGS) 2, a GTPase-activating protein, is activated via the nitric oxide (NO)-cGMP pathway and thereby may influence blood pressure regulation. To test that notion, we measured mean arterial blood pressure (MAP) and heart rate (HR) with telemetry in N(omega)-nitro-l-arginine methyl ester (l-NAME, 5 mg l-NAME/10 ml tap water)-treated RGS2-deficient (RGS2(-/-)) and RGS2-sufficient (RGS2(+/+)) mice and assessed autonomic function. Without l-NAME, RGS2(-/-) mice showed during day and night a similar increase of MAP compared with controls. l-NAME treatment increased MAP in both strains. nNOS is involved in this l-NAME-dependent blood pressure increase, since 7-nitroindazole increased MAP by 8 and 9 mmHg (P < 0.05) in both strains. The l-NAME-induced MAP increase of 14-15 mmHg during night was similar in both strains. However, the l-NAME-induced MAP increase during the day was smaller in RGS2(-/-) than in RGS2(+/+) (11 +/- 1 vs. 17 +/- 2 mmHg; P < 0.05). Urinary norepinephrine and epinephrine excretion was higher in RGS2(-/-) than in RGS2(+/+) mice. The MAP decrease after prazosin was more pronounced in l-NAME-RGS2(-/-). HR variability parameters [root mean square of successive differences (RMSSD), low-frequency (LF) power, and high-frequency (HF) power] and baroreflex sensitivity were increased in RGS2(-/-). Atropine and atropine plus metoprolol markedly reduced RMSSD, LF, and HF. Our data suggest an interaction between RGS2 and the NO-cGMP pathway. The blunted l-NAME response in RGS2(-/-) during the day suggests impaired NO signaling. The MAP increases during the active phase in RGS2(-/-) mice may be related to central sympathetic activation and increased vascular adrenergic responsiveness.

Effect of Benzodiazepine Hypnotic Triazolam on Relationship of Blood Pressure and Paco2to Cerebral Blood Flow During Human Non-Rapid Eye Movement Sleep

We sought to clarify the effect of short-acting benzodiazepine hypnotic on the relationship of arterial blood pressure and arterial partial pressure of carbon dioxide (Paco2) to regional cerebral blood flow (rCBF) during human non-rapid-eye-movement (non-REM) sleep. Nine young normal volunteers were treated in a randomized, crossover design with triazolam or placebo and underwent positron emission tomography at night. During wakefulness and stage 2 and slow wave (stages 3 and 4) sleep, we measured mean arterial blood pressure (MAP), Paco2, and absolute CBF. With triazolam compared to placebo, MAP reduced gradually. During stage 2 sleep, Paco2 increased and whole-brain mean CBF decreased. With triazolam, relative rCBF of the left orbital basal forebrain decreased more during stage 2 than slow wave sleep, whereas absolute CBF of the occipital cortex and cerebral white matter remained constant. During triazolam-induced stage 2 sleep, absolute CBF of the cerebral white matter correlated more strongly to both MAP and Paco2 than during placebo sleep and also correlated more strongly to both MAP and Paco2 than absolute CBF of the occipital cortex. In the frontal white matter, during triazolam-induced stage 2 sleep compared to wakefulness, absolute CBF was significantly better correlated to MAP, but not to Paco2. During triazolam-induced stage 2, the cerebral white matter may receive a modulated CBF regulation having the strengthened relationship of Paco2 to CBF and, more locally, the frontal white matter may depend precariously on CBF regulation.

24-h blood pressure monitoring in normal tension glaucoma: night-time blood pressure variability

Systemic arterial hypotension, hypertension and altered ocular blood flow are known risk factors in glaucoma. In this study, 24-h ambulatory blood pressure monitoring was performed in patients with normal tension glaucoma (NTG) and controls to evaluate blood pressure variability. In all, 51 patients with NTG and 28 age-matched controls were included in this prospective study. A 24-h ambulatory blood pressure monitoring (SpaceLabs Medical Inc., Redmond, USA) was performed and systolic, diastolic and mean arterial blood pressures were measured every 30 min during daytime (0800-2000) and night time (0000-0600). To evaluate blood pressure variability a variability index was defined as the s.d. of blood pressure measurements. Night-time blood pressure depression ('dip') was calculated (in percent of the daytime blood pressures). Patients with NTG exhibited higher night-time diastolic (P = 0.01) and mean arterial blood pressure values (P = 0.02) compared to controls, whereas systolic blood pressure data were not significantly different. The variability indices of night-time systolic, diastolic and mean arterial blood pressure measurements were significantly increased in patients with NTG compared to controls (P < 0.05). The night-time blood pressure depression of systolic (P = 0.47), diastolic (P = 0.11) and mean arterial blood pressures (P = 0.28) was not significantly different between patients with NTG and controls. In conclusion, patients with NTG showed increased variability of night-time blood pressure measurements compared to controls. Increased fluctuation of blood pressure may lead to ocular perfusion pressure fluctuation and may cause ischaemic episodes at the optic nerve head.

Differential role of the paraventricular nucleus of the hypothalamus in modulating the sympathoexcitatory component of peripheral and central chemoreflexes

In the present study we investigated the involvement of the hypothalamic paraventricular nucleus (PVN) in the modulation of sympathoexcitatory reflex activated by peripheral and central chemoreceptors. We measured mean arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) before and after blocking neurotransmission within the PVN by bilateral microinjection of 2% lidocaine (100 nl) during specific stimulation of peripheral chemoreceptors by potassium cyanide (KCN, 75 microg/kg iv, bolus dose) or stimulation of central chemoreceptors with hypercapnia (10% CO(2)). Typically stimulation of peripheral chemoreceptors evoked a reflex response characterized by an increase in MAP, RSNA, and PNA and a decrease in HR. Bilateral microinjection of 2% lidocaine into the PVN had no effect on basal sympathetic and cardiorespiratory variables; however, the RSNA and PNA responses evoked by peripheral chemoreceptor stimulation were attenuated (P < 0.05). Bilateral microinjection of bicuculline (50 pmol/50 nl, n = 5) into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation (P < 0.05). Conversely, the GABA agonist muscimol (0.2 nmol/50 nl, n = 5) injected into the PVN attenuated these reflex responses (P < 0.05). Blocking neurotransmission within the PVN had no effect on the hypercapnia-induced central chemoreflex responses in carotid body denervated animals. These results suggest a selective role of the PVN in processing the sympathoexcitatory and ventilatory component of the peripheral, but not central, chemoreflex.

Cocaine and Subarachnoid Hemorrhage

Object. The goal of this study was to analyze the relationship between cocaine use and outcomes of aneurysmal subarachnoid hemorrhage (SAH). Methods. A retrospective review was performed of the medical records of patientswith intracranial aneurysms treated at a single institution between January 1996 and December 2001. Only patients who presented with SAH were included in the study. The covariates chosen for the statistical analysis included the following: patient age, sex, and race; systolic and mean arterial blood pressure measurements on hospital admission; Hunt and Hess and Fisher grades; preexistent major systemic disease; and history of alcohol, tobacco, or cocaine use. The Glasgow Outcome Scale (GOS) was used to standardize outcome and was dichotomized such that a score between 1 and 3 was considered a poor outcome and a score of 4 or 5 was considered a favorable outcome. The records of 151 patients were reviewed and 108 of these presented with aneurysmal SAH. Of these 108 patients, 36 (33.3%) had used cocaine within 24 hours before presentation. A Hunt and Hess grade of IV or V was assigned to 20 (55.6%) of 36 patients who used cocaine, compared with eight (11.1%) of 72 patients who did not; this difference was found to be statistically significant (p < 0.0001). Twenty-eight patients (77.8%) in the cocaine user group and 20 patients (27.8%) in the non-cocaine user group experienced clinically significant, angiographically confirmed vasospasm during their hospital course (p < 0.0001). Cocaine use was associated with a 2.8-fold greater risk of developing vasospasm (95% confidence interval [CI] 1.86-4.22). A GOS score of 1, 2, or 3 was assigned to 33 patients (91.7%) in the cocaine user group and to 20 patients (27.8%) in the non-cocaine user group (p < 0.0001). Cocaine use was associated with a 3.3-fold greater risk of poor outcome (95% CI 2.24-4.85). This association was found to be independent of Hunt and Hess grade as well as of vasospasm. Conclusions. Cocaine adversely affects both the presentation of and outcome in patients with aneurysmal SAH who are undergoing treatment for this disease. The vasoactive properties of the drug appear to aggravate the already tenuous situation of SAH and increase both the occurrence and influence of cerebral vasospasm. Statistical analysis demonstrates that cocaine directly affects both presentation and outcome in a significant manner. It is the authors' interpretation of the results of this retrospective review that cocaine use negatively affects outcome to such an extent that it should be considered equal to the presence of a major systemic illness when determining Hunt and Hess grade.

Effects of early perturbation of the renin–angiotensin system on cardiovascular remodeling in spontaneously hypertensive rats

Rationale The goal of this study was to analyze cardiovascular (CV) remodeling in early, short-term CAP treated SHR and their offspring. Methods We treated SHR with Captopril (CAP, 100 mg/kg) from in utero to 1 month of age (OCAP). Some of these rats were mated at 3–4 months of age and we used their offspring (2nd G). Controls were untreated SHR, normotensive Wistar Kyoto rats (WKY) and SHR maintained on CAP (SCAP). At 12–14 months of age, rats were cannulated for mean arterial blood pressure (MAP) measurements. An image analysis system was used to quantitate changes in cardiac and vascular (wall-to-lumen ratios, w/l) morphology and fibrosis. Results Early, short-term CAP treatment prevented the full expression of hypertension in treated rats and their offspring. MAPs were: SHR (180 ± 2.2 mm Hg); WKY 125 ± 3 mm Hg); SCAP 112 ± 2.5mm Hg; OCAP 138 ± 2.3 mm Hg; and 2nd G (145 ± 2.0 mm Hg). There were significant decreases in heart weight/body weight ratios, large and small vessel morphology, and interstitial and perivascular fibrosis in CAP-treated animals and their offspring in comparison to untreated SHR. Conclusions The CV protective properties of early, short-term CAP treatment were not solely due to a reduction in MAP. Although MAP was higher in OCAP and 2nd G, CV structure resembled that found in WKY and SCAP. The effects of our early treatment appear to be due to chronic blockade of the renin–angiotensin system and its effects on growth of CV tissues and the development of fibrosis.

Arterial blood pressure monitoring in overweight critically ill patients: invasive or non-invasive?

PURPOSE: Systolic (SBP), diastolic (DBP), and mean (MAP) arterial blood pressure measurements frequently guide management in intensive care. Direct readings, commonly from a major artery, are considered to be the gold standard. Since arterial cannulation is associated with risks, alternative non-invasive blood pressure (NIBP) measurements are routinely used. However, the accuracy of NIBP in overweight patients in the outpatient setting is variable and little is known about critically ill patients. This study was performed to compare direct intra-arterial BP (IABP) to NIBP measurements obtained using auscultatory and oscillometric methods in overweight critically ill patients.

Reoxygenation with 100 or 21% Oxygen after Cerebral Hypoxemia-Ischemia-Hypercapnia in Newborn Piglets

We tested if reoxygenation with 100% O₂ was superior to 21% O₂ after combined cerebral hypoxemia-ischemia-hypercapnia (HIH) in newborn piglets. Twenty-eight piglets were randomized to reoxygenation with 100 or 21% O₂ following asphyxia. Asphyxia was induced by ventilation with 8% O₂, adding CO₂, and temporary occlusion of both common carotid arteries. After 20 min, reoxygenation-reperfusion was started with 21% O₂ (HIH 21% group, n = 13) or 100% O₂ (HIH 100% group, n = 11) for 30 min followed by 21% O₂. All piglets were observed for 2 h. We measured mean arterial blood pressure (MABP), changes in microcirculation in the cerebral cortex (laser Doppler), and extracellular concentrations of hypoxanthine in the cortex and amino acids in the striatum (microdialysis). We found significantly higher MABP and better restoration of microcirculation after reoxygenation with 100% compared with 21% O₂, but no differences in biochemical markers were found between the groups. This indicates that the brain tolerated reoxygenation with 21% as well as with 100% O₂ in the present model of experimental asphyxia in spite of the differences in MABP and cerebral microcirculation.

Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule.

The purpose of this study was to evaluate the physiological significance of a tissue renin-angiotensin system in the proximal tubule of the kidney. To accomplish this, we produced mice that express human renin (hREN) under the control of the kidney androgen-regulated promoter (KAP), which is androgen responsive. One of the lines expressed the hREN transgene primarily in the kidney. Renal expression of the transgene was undetectable in females but could be induced by testosterone treatment. Because the renin-angiotensin system is species specific, we bred KAP2-hREN mice with the mice expressing human angiotensinogen under the same promoter (KAP-hAGT) to produce offspring that expressed both transgenes. We measured mean arterial blood pressure (MAP) in the carotid artery of double-transgenic and control mice using radiotelemetry. Double-transgenic female mice had a normal baseline MAP (116 +/- 4 mmHg, n = 8), which increased by 15 mmHg after 2 wk of testosterone treatment, and returned to baseline after elimination of the testosterone pellet. The change in arterial pressure paralleled the change in plasma testosterone. There was no MAP change in testosterone-treated control littermates. We conclude that dual production of renin and angiotensinogen in the renal proximal tubule can result in a systemic increase in arterial pressure. These data support a role for a tissue-specific renin-angiotensin system in the renal proximal tubule that contributes to the regulation of systemic blood pressure.

Cocaine use as a predictor of outcome in aneurysmal subarachnoid hemorrhage.

The goal of this study was to analyze the relationship between cocaine use and outcomes of aneurysmal subarachnoid hemorrhage (SAH). A retrospective review was performed of the medical records of patients with intracranial aneurysms treated at a single institution between January 1996 and December 2001. Only patients who presented with SAH were included in the study. The covariates chosen for the statistical analysis included the following: patient age, sex, and race; systolic and mean arterial blood pressure measurements on hospital admission; Hunt and Hess and Fisher grades; pre-existent major systemic disease; and history of alcohol, tobacco, or cocaine use. The Glasgow Outcome Scale (GOS) was used to standardize outcome and was dichotomized such that a score between 1 and 3 was considered a poor outcome and a score of 4 or 5 was considered a favorable outcome. The records of 151 patients were reviewed and 108 of these presented with aneurysmal SAH. Of these 108 patients, 36 (33.3%) had used cocaine within 24 hours before presentation. A Hunt and Hess grade of IV or V was assigned to 20 (55.6%) of 36 patients who used cocaine, compared with eight (11.1%) of 72 patients who did not; this difference was found to be statistically significant (p < 0.0001). Twenty-eight patients (77.8%) in the cocaine user group and 20 patients (27.8%) in the non-cocaine user group experienced clinically significant, angiographically confirmed vasospasm during their hospital course (p < 0.0001). Cocaine use was associated with a 2.8-fold greater risk of developing vasospasm (95% confidence interval [CI] 1.86-4.22). A GOS score of 1, 2, or 3 was assigned to 33 patients (91.7%) in the cocaine user group and to 20 patients (27.8%) in the non-cocaine user group (p < 0.0001). Cocaine use was associated with a 3.3-fold greater risk of poor outcome (95% CI 2.24-4.85). This association was found to be independent of Hunt and Hess grade as well as of vasospasm. Cocaine adversely affects both the presentation of and outcome in patients with aneurysmal SAH who are undergoing treatment for this disease. The vasoactive properties of the drug appear to aggravate the already tenuous situation of SAH and increase both the occurrence and influence of cerebral vasospasm. Statistical analysis demonstrates that cocaine directly affects both presentation and outcome in a significant manner. It is the authors' interpretation of the results of this retrospective review that cocaine use negatively affects outcome to such an extent that it should be considered equal to the presence of a major systemic illness when determining Hunt and Hess grade.