Reduction In Systolic Arterial Pressure Research Articles

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits.

Meta-Analysis of Randomized Controlled Trials Using Tool-Assisted Target Weight Adjustments in Chronic Dialysis Patients

IntroductionTechnological adjuncts have been developed to improve the accuracy of fluid removal goals in maintenance dialysis recipients. We aimed to determine whether the introduction of these tools has been shown to impact clinical outcomes.MethodsWe performed a systematic review and meta-analysis of randomized controlled trials that compared fluid management guided by technological adjuncts to standard care in hemodialysis and peritoneal dialysis. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular events, hospitalizations, intradialytic hypotension, blood pressure, symptoms, antihypertensive medications. and left ventricular mass index.ResultsOf the 2940 citations retrieved, we identified a total of 12 eligible trials comprising 2406 participants. In the 10 studies (n = 2111) with data on mortality, the use of adjunct technologies was not associated with a reduction of mortality (rate ratio [RR]: 0.92; confidence interval [CI]: 0.57–1.51; I2 = 36%). The intervention conferred a reduction in systolic arterial pressure (mean difference: −3.14; CI: −5.89 to −0.38; I2 = 39%) but did not affect other outcomes. In a subgroup analysis, bioimpedance was associated with a reduced risk of hospitalization (RR: 0.68; CI: 0.46–0.99; I2 = 55%). The risk of bias was high or unclear in most studies and the quality of evidence was judged to be low.ConclusionsAmong maintenance dialysis recipients, technological adjuncts for fluid management did not improve survival. Trials mostly investigated the use of bioimpedance, whereas the evidence for use of other technologies remain very scarce. Future adequately powered trials should assess a broader array of promising technologies using meaningful clinical outcomes over a prolonged follow-up duration.

Relationships between orthostatic hypotension, frailty, falling and mortality in elderly care home residents

BackgroundOrthostatic hypotension (OH; profound falls in blood pressure when upright) is a common deficit that increases in incidence with age, and may be associated with falling risk. Deficit accumulation results in frailty, regarded as enhanced vulnerability to adverse outcomes. We aimed to evaluate the relationships between OH, frailty, falling and mortality in elderly care home residents.MethodsFrom the Minimum Data Set (MDS) document, a frailty index (FI-MDS) was generated from a list of 58 deficits, ranging from 0 (no deficits) to 1.0 (58 deficits). OH was evaluated from beat-to-beat blood pressure and heart rate (finger plethysmography) collected during a 15-min supine-seated orthostatic stress test. Retrospective and prospective falling rates (falls/year) were extracted from facility falls incident reports. All-cause 3-year mortality was determined. Data are reported as mean ± standard error.ResultsData were obtained from 116 older adults (aged 84.2 ± 0.9 years; 44% males) living in two long term care facilities. The mean FI-MDS was 0.36 ± 0.01; FI-MDS was correlated with age (r = 0.277; p = 0.003). Those who were frail (FI ≥ 0.27) had larger Initial (− 17.8 ± 4.2 vs − 6.1 ± 3.3 mmHg, p = 0.03) and Consensus (− 22.7 ± 4.3 vs − 11.5 ± 3.3 mmHg, p = 0.04) orthostatic reductions in systolic arterial pressure. Frail individuals had higher prospective and retrospective falling rates and higher 3-year mortality. Receiver operating characteristic curves evaluated the ability of FI-MDS alone to predict prospective falls (sensitivity 72%, specificity 36%), Consensus OH (sensitivity 68%, specificity 60%) and 3-year mortality (sensitivity 77%, specificity 49%). Kaplan Meier survival analyses showed significantly higher 3-year mortality in those who were frail compared to the non-frail (p = 0.005).ConclusionsFrailty can be captured using a frailty index based on MDS data in elderly individuals living in long term care, and is related to susceptibility to orthostatic hypotension, falling risk and 3-year mortality. Use of the MDS to generate a frailty index may represent a simple and convenient risk assessment tool for older adults living in long term care. Older adults who are both frail and have impaired orthostatic blood pressure control have a particularly high risk of falling and should receive tailored management to mitigate this risk.

Identification of new bioactive peptides from Kefir milk through proteopeptidomics: Bioprospection of antihypertensive molecules

Kefir, a probiotic beverage prepared from fermented milk, has been associated with antihypertensive activity. However, the bioactive molecules responsible for this activity still remain unclear. Therefore, in this study we aim to evaluate the mechanisms of the antihypertensive effects of Kefir in the two-kidney one-clip hypertension model, and to bioprospect for bioactive peptides identified by proteomic methodologies. Treatment with Kefir was performed via gavage, and resulted in a 37 mmHg reduction in systolic arterial pressure and 19% inhibition of angiotensin converting enzyme (ACE) activity. For the proteopeptidomic study, the protein extract of Kefir beverage and non-fermented bovine milk were analysed by MALDI-TOF mass spectrometry, and their tryptic digestion products sequenced via Shotgun proteomics (Q-Exactive mass spectrometer). A list of 35 peptides with potential hypertensive activity due to ACE inhibition were identified. These results demonstrate the benefits of Kefir products, and may guide the design of new antihypertensive drugs.

Oral treatment with Euterpe oleracea Mart. (açaí) extract improves cardiac dysfunction and exercise intolerance in rats subjected to myocardial infarction.

BackgroundThis study was designed to evaluate the cardioprotective effects of Euterpe oleracea Mart., popularly known as “açaí”, on rats subjected to myocardial infarction (MI).MethodsHydroalcoholic extracts of açaí were obtained from a decoction of the seeds. Two male Wistar rat groups were delineated: 1) the sham-operated group (control, n = 6), with no surgical amendment, and 2) the MI group (n = 12), in which the anterior descendent coronary artery was occluded during surgery. MI group was divided into two subgroups, in which rats were either treated with hydroalcoholic extract of Euterpe oleracea seeds (100 mg/kg/day p.o.) or received no treatment. Treatment began on the day of surgery, and lasted 4 weeks. Subsequently, rats were subject to an exercise test protocol, hemodynamic evaluation, and histological analysis of the left ventricle. Groups were compared using one-way analysis of variance (ANOVA), followed by Dunnett’s test.ResultsThe total running distance of sham rats was 1339.0 ± 276.6 m, MI rats was 177.6 ± 15.8 m (P < 0.05), and MI-açaí rats was 969.9 ± 362.2 m. Systolic arterial pressure was significantly decreased in MI rats (86.88 ± 4.62 mmHg) compared to sham rats (115.30 ± 7.24 mmHg; P < 0.05). Açaí treatment prevented a reduction in systolic arterial pressure (130.00 ± 8.16 mmHg) compared to MI rats (P < 0.05). Left ventricular (LV) end-diastolic pressure was significantly augmented in MI rats (17.62 ± 1.21 mmHg) compared to sham rats (4.15 ± 1.60 mmHg; P < 0.05), but was 3.69 ± 2.69 mmHg in açaí-treated rats (P < 0.05 vs. MI). The LV relaxation rate (-dp/dt) was reduced in MI rats compared to the sham group, whereas açaí treatment prevented this reduction. Açaí treatment prevented cardiac hypertrophy and LV fibrosis in MI rats.ConclusionsEuterpe oleracea treatment of MI rats prevented the development of exercise intolerance, cardiac hypertrophy, fibrosis, and dysfunction.

Pharmacology of Milrinone in Neonates With Persistent Pulmonary Hypertension of the Newborn and Suboptimal Response to Inhaled Nitric Oxide*

Persistent pulmonary hypertension of the newborn is a common problem with significant morbidity and mortality. Inhaled nitric oxide is the standard care, but up to 40% of neonates are nonresponders. Milrinone is a phosphodiesterase III inhibitor which increases the bioavailability of cyclic adenosine monophosphate and has been shown to improve pulmonary hemodynamics in animal experimental models. The primary objective was to investigate the pharmacological profile of milrinone in persistent pulmonary hypertension of the newborn. Secondary objectives were to delineate short-term outcomes and safety profile. An open label study of milrinone in neonates with persistent pulmonary hypertension of the newborn was conducted. Patients received an intravenous loading dose of milrinone (50 μg/kg) over 60 mins followed by a maintenance infusion (0.33-0.99 μg/kg/min) for 24-72 hrs. Physiologic indices of cardiorespiratory stability and details of cointerventions were recorded. Serial blood milrinone levels were collected after the bolus, following initiation of the maintenance infusion to determine steady state levels, and following discontinuation of the drug to determine clearance. Echocardiography was performed before and after (1, 12 hrs) milrinone initiation. Milrinone. Eleven neonates with a diagnosis of persistent pulmonary hypertension of the newborn who met eligibility criteria were studied. The median (SD) gestational age and weight at birth were 39.2 ± 1.3 wks and 3481 ± 603 g. The mean (± sd) half-life, total body clearance, volume of distribution, and steady state concentration of milrinone were 4.1 ± 1.1 hrs, 0.11 ± 0.01 L/kg/hr, 0.56 ± 0.19 L/kg, and 290.9 ± 77.7 ng/mL. The initiation of milrinone led to an improvement in PaO2 (p = 0.002) and a sustained reduction in FIO2 (p < 0.001), oxygenation index (p < 0.001), mean airway pressure (p = 0.03), and inhaled nitric oxide dose (p < 0.001). Although a transient reduction in systolic arterial pressure (p < 0.001) was seen following the bolus, there was overall improvement in base deficit (p = 0.01) and plasma lactate (p = 0.04) with a trend towards lower inotrope score. Serial echocardiography revealed lower pulmonary artery pressure, improved right and left ventricular output, and reduced bidirectional or right-left shunting (p < 0.05) after milrinone treatment. The pharmacokinetics of milrinone in persistent pulmonary hypertension of the newborn is consistent with published data. The administration of intravenous milrinone led to better oxygenation and improvements in pulmonary and systemic hemodynamics in patients with suboptimal response to inhaled nitric oxide. These data support the need for a randomized controlled trial in neonates.

Spirituality and religiosity in combating pain

The International Association for the Study of Pain defines pain as an unpleasant sensory and emotional experience, peculiar,specific and non transferable associated with actual or potential tissue damage. Pain, especially when chronic, affects all areas of life ofindividuals, being thus physical, psychic, and social. Amongst the forms for combating pain, religiosity and spirituality has proved to beimportant for sick people, and are related to the reduction of stress pain involves. The role and the mechanisms by which religiosity andspirituality act in combating chronic pain were the object of a literature survey in Medline database. Religiosity is characterized as thefirst or the second strategy used against pain. Religious and spiritual individuals present a reduction of pain complaints, of the concentrationof ACTH (adrenocorticotropic hormone) and serous cortisol, a reduction of systolic arterial pressure, and cardiac and respiratoryfrequency. Religious activities produce an increase of the activation of prefrontal cortex, causing a higher efficiency and interactivity ofhypothalamic-pituitary-adrenal system. The increase of pain mediators involved also occurs: GABA, serotonin and dopamine. Spiritualindividuals face pain better, especially chronic pain, due to physiological and neural alterations coming from their beliefs.

Can human cardiovascular regulation during exercise be learnt from feedback from arterial baroreceptors?

During dynamic exercise, a large fall in systemic vascular resistance occurs. Arterial pressure (AP) is, however, maintained through a combination of central command and neural activity from muscle afferents that adjust the autonomic outflow to the circulation. How these signals are calibrated to provide accurate regulation of AP remains unclear. This study tests the hypothesis that the calibration can be ‘learnt’ through feedback from the arterial baroreceptors arising over multiple trials of exercise. Eight healthy subjects undertook three different protocols in random order. The test protocol consisted of 7 days' training, when subjects were exposed on 70 occasions to 4 min of exercise (50% of maximal oxygen uptake capacity) paired with neck suction (−40 mmHg) to mimic an excessive rise in AP at the carotid baroreceptors with exercise. Two control protocols involved training with either exercise or neck suction alone. No significant changes in mean AP, diastolic AP or heart rate during normal exercise were detected following training with any protocol. However, the rise in systolic AP with exercise was attenuated by an average of 7.3 ± 2.0 mmHg (mean ± s.e.m., P < 0.01) on the first and second days following training with the test protocol, but not with either control protocol (P < 0.05 for difference between protocols, ANOVA). In conclusion, this study failed to show that mean AP during normal exercise could be reduced through prior conditioning by overstimulation of the baroreceptors during exercise. However, a reduction in systolic AP was observed that suggests the presence of some plasticity within the autonomic response, consistent with our hypothesis.

A prospective, randomized, blinded comparison between continuous thoracic paravertebral and epidural infusion of 0.2% ropivacaine after lung resection surgery

The aim of this prospective, randomized, blinded study was to compare analgesic efficacy of continuous paravertebral and epidural analgesia for post-thoracotomy pain. Forty-two ASA physical status II-III patients undergoing lung resection surgery were randomly allocated to receive post-thoracotomy analgesia with either a thoracic epidural (group EPI, n = 21) or paravertebral (group PVB, n = 21) infusion of 0.2% ropivacaine (infusion rate: 5-10 mL h-1). The degree of pain at rest and during coughing, haemodynamic variables and blood gas analysis were recorded every 12 h for the first 48 h. The area under the curve of the visual analogue pain score during coughing over time was 192 (60-444) cm h-1 in group EPI and 228 (72-456) cm h-1 in group PVB (P = 0.29). Rescue morphine analgesia was required in four patients of group EPI (19%) and five patients of group PVB (23%) (P = 0.99). The PaO2/FiO2 ratio reduced significantly from baseline values in both groups without between-group differences. The median (range) percentage reduction of systolic arterial pressure from baseline was -9 (0 to -9)% in group PVB and -17 (0 to -38)% in group EPI (P = 0.02); while clinically relevant hypotension (systolic arterial pressure decrease >30% of baseline) was observed in four patients of group EPI only (19%) (P = 0.04). Patient satisfaction with the analgesia technique was 8.5 (8-9.8) cm in group EPI and 9 (7.5-10) cm in group PVB (P = 0.65). Continuous thoracic paravertebral analgesia is as effective as epidural blockade in controlling post-thoracotomy pain, but is associated with less haemodynamic effects.

Evidence of decreased sympathetic function in children with psychosomatic symptoms.

We investigated cardiovascular autonomic function using power spectral analysis of heart rate variation and beat-to-beat finger arterial pressure at rest and while standing and correlated these findings with self-reported psychosomatic and psychosocial symptoms in 122 schoolchildren. Children with three or more psychosomatic and psychosocial symptoms (somatizers) were found to have significantly lower blood pressure than children without symptoms. Somatizers had the more decreased spectral power of the low frequency (LF) band of arterial pressure and RR intervals in the supine position. The high frequency (HF) power did not differ between the two groups. Somatizers showed a more marked reduction in systolic arterial pressure at the onset of standing than did subjects without symptoms but somatizers showed an identical response in systolic arterial pressure when compared to subjects without symptoms during the later stage of standing. The increases in the LF band of arterial pressure and LF/HF of RR intervals during standing were higher in somatizers. These results suggest that somatizers have decreased sympathetic modulation. We conclude that psychosomatic and psychosocial symptoms in children might be associated with low blood pressure and decreased sympathetic modulation.

Instantaneous orthostatic hypotension in children and adolescents: a new entity of orthostatic intolerance.

We are the first to report clinical characteristics and circulatory and catecholamine responses to postural change in 44 children with instantaneous orthostatic hypotension (INOH). The symptoms include chronic fatigue, orthostatic dizziness, weakness, sleep disturbance, syncope or near syncope, headache, and loss of appetite. We divided the patients into two groups: group I (30 patients) had either a recovery time for mean arterial pressure of >25 s or a recovery time of >20 s with a 60% or greater decrease in mean arterial pressure at the initial decrease; group II (14 patients) had a prolonged reduction in systolic arterial pressure of > 15% during the later stage of standing (3-7 min) in addition to the criteria for group I. INOH was characterized by a marked reduction in blood pressure at the initial decrease (mean, -55/-27 mm Hg systolic/diastolic). Delayed recovery time of >60 s was found in 21 of 44 patients and orthostatic tachycardia (>35 beats per minute) in 20 of 44. Plasma noradrenaline responses were significantly lower in group I and II than in controls at 1 min of standing and were lower in group II at 5 min of standing. These results suggest that mechanisms responsible for INOH may depend on insufficient sympathetic activation during standing, possibly due to centrally mediated sympathetic inhibition, thus causing impairment of quality of life including school absenteeism. INOH is an important pathologic condition in children with complaints of orthostatic intolerance and can be an unrecognized cause of chronic fatigue. This condition can be identified by using a noninvasive beat-to-beat continuous blood pressure monitoring system.

Hypotension During Subarachnoid Anesthesia

Comment Hypotension after subarachnoid block performed for fixation of a fractured hip is a common problem for anesthesiologists. Critchley et al. examine the effects of large doses of ephedrine alone or ephedrine plus colloid to treat hypotension in this fragile population of patients. Both groups showed reductions in systolic arterial pressure and systemic vascular resistance after subarachnoid block. However, in the group receiving ephedrine alone, the central venous pressure (CVP) and stroke index decreased, whereas heart rate increased. In contrast, CVP and stroke index increased in the group receiving ephedrine plus colloid; heart rate also in-

Spinal anaesthesia for transurethral surgery: comparison of 2% lignocaine with hyperbaric 0.5% bupivacaine

We have compared 2% lignocaine 3.5 ml with 0.5% hyperbaric bupivacaine 3 ml in a randomized, double-blind study in 30 patients undergoing subarachnoid anaesthesia for transurethral surgery. A sensory level of T10 was produced more quickly (P = 0.0001) and maximum height reached sooner (P = 0.0002) with lignocaine, although there was a greater reduction in systolic arterial pressure (P = 0.03) and a trend towards slower heart rates (P = 0.056). Return of full sensory and motor function occurred earlier with lignocaine (P = 0.00005 and P = 0.02).

Induction of anaesthesia with eltanolone at different rates of infusion in elderly patients

We have determined the effective dose of eltanolone (pregnanolone) required to induce anaesthesia in 30 ASA I and II patients aged 60 yr and over. Eltanolone 4 mg ml-1 was administered at a rate of 300 ml h-1 (group 1), 600 ml h-1 (group 2) or 1200 ml h-1 (group 3) until loss of consciousness, as judged by loss of verbal contact with the patient. Anaesthesia was induced successfully in all patients. The slower rates of induction were associated with a significant increase in induction time (ANOVA, P < 0.01) and a decrease in the induction dose (P < 0.01). There was a significant reduction in systolic arterial pressure after induction of anaesthesia in groups 2 and 3 (MANOVA, P < 0.01). This study suggests that the induction dose of eltanolone in unpremedicated older patients should not exceed 0.6 mg kg-1.

Effect of captopril on sympathetic preganglionic efferent activity in cats

In 13 decerebrate cats, we studied the effects of captopril (10 mg/kg iv bolus) on the background discharge of thoracic preganglionic sympathetic fibers. After drug administration there was an initial reduction in systolic arterial pressure (SAP), which was followed by a later inhibition of sympathetic discharge (from 2.7 +/- 0.5 to 0.79 +/- 0.1 imp/0.1 s; P < 0.01). Captopril significantly reduced the excitatory response of sympathetic fibers to premature ventricular contraction (70 +/- 17 vs. 257 +/- 30%), inferior vena cava obstruction (176 +/- 56 vs. 315 +/- 85%) and asphyxia (143 +/- 20 vs. 245 +/- 51%). Vice versa the sympathetic response to aortic occlusion was unaffected (-58 +/- 8 vs. -62 +/- 6%). A similar reduction in sympathetic discharge was observed after captopril administration in anesthetized cats (n = 3). On the contrary, no changes in background neural discharge were noticed in decerebrate-spinalized cats (n = 5), despite comparable hemodynamic effects. These data indicate that captopril reduces sympathetic efferent activity and its responsiveness to excitatory stimuli. The lack of neural effects in decerebrate-spinalized cats is consistent with a brain stem site of action of captopril.

Acute Cardiovascular Responses to Internal Carotid Artery Occlusion During Carotid Endarterectomy and to the Restoration of Internal Carotid Flow

Heart rate, central venous pressure, radial artery pressure and electrocardiograph were recorded in 14 patients undergoing carotid endarterectomy under general anaesthesia supplemented with fentanyl and halothane and muscle relaxation as required. Induction of anaesthesia was followed by a significant reduction in systolic arterial pressure and a rise in central venous pressure (CVP). Thereafter CVP did not vary significantly and heart rate did not change significantly at any stage. After internal carotid artery occlusion, mean systolic pressure at one minute, 143 (SD 17) mmHg, and three minutes, 160 (SD 27) mmHg, were both significantly higher than prior to occlusion, 132 (SD 17) mmHg (P less than 0.01 and P less than 0.002 respectively). Similar significant changes occurred in diastolic pressure after carotid occlusion (P less than 0.02 and P less than 0.002 respectively). The restoration of flow through the internal carotid artery in patients operated on without a shunt was associated with a significant reduction in mean systolic pressure. The mean systolic pressure at one minute, 145 (SD 20) mmHg, and three minutes, 135 (SD 19) mmHg, were both significantly lower than that before restoration of flow, 159 (SD 17) mmHg (P less than 0.02 and P less than 0.05 respectively). Changes in mean diastolic pressure in this group at these times, while in the same direction, were not significant. The observed hypertensive response to carotid occlusion may assist in preserving cerebral perfusion while the internal carotid artery is occluded, but may be hazardous for patients with ischaemic heart disease.

Thymectomy delays the development of hypertension in Okamoto spontaneously hypertensive rats.

Previous studies in rats have demonstrated that immune system dysfunction contributes to the aetiology of spontaneous hypertension. Chronic immunosuppression with cyclophosphamide attenuated the level of hypertension in Okamoto spontaneously hypertensive rats (SHR) by approximately 50%. Also, neonatal thymic implants delayed the development of spontaneous hypertension and significantly attenuated its level at the age of 22 weeks in SHR. In the present study, the effect of thymectomy at the age of 4 weeks on blood pressure was investigated in SHR and Wistar-Kyoto (WKY) rats. The removal of the thymus gland in 4-week-old SHR produced a significant reduction in systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) when rats were 16-19 weeks old, while no pressure reduction was observed in WKY rats. The decrease in arterial pressure of 16-week-old SHR was associated with a significant reduction in lymphocyte count at this age as compared with the control group. In 1-year-old SHR, thymectomized at the age of 4 weeks, there was no significant difference in arterial pressure or lymphocyte count compared with controls. These data support the hypothesis that an immune imbalance may be important in the development of spontaneous hypertension. We conclude that thymectomy at a young age (4 weeks) delays the development of hypertension in SHR.

Effect of indoramin, labetalol and alinidine on sympathetic function in normal man.

The effects of single oral doses of indoramin (mean dose 58 mg), abetalol (mean dose 150 mg), alinidine 80 mg and placebo on arterial pressure and heart rate in the supine and standing positions were studied in six normal volunteers. Doses were chosen to give equivalent reductions of arterial pressure in the standing position. Observations were made before and at 2 and 4 h after drug administration. Plasma noradrenaline (NA) was measured at each time interval in the supine position, and after 4 min of standing. Plasma renin activity (PRA) was measured at each time interval after 30 min in the standing position. In the supine position, alinidine produced a significant reduction of systolic arterial pressure from 124.0 +/- 3.0 mm Hg to 104.3 +/- 4.1 mm Hg at 2 h (P less than 0.01) and to 101.7 +/- 2.2 mm Hg at 4 h (P less than 0.01). Diastolic pressure was reduced from 74.7 +/- 2.6 mm Hg to 57.0 +/- 4.6 mm Hg at 4 h (P less than 0.01). Arterial pressure was unchanged after indoramin or labetalol administration. In the supine position, heart rate was unchanged after indoramin, and small reductions were observed after labetalol and alinidine. Indoramin produced a significant increase in plasma NA. A small increase of plasma NA was observed after labetalol, and a small decrease after alinidine. In the standing position, the three active drugs reduced systolic arterial pressure to a similar extent (indoramin, -26.7 mm Hg at 4 h after drug administration; labetalol, -21.3 mm Hg at 2 h; alinidine, -21.7 mm Hg at 4 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic activity in systolic hypertension.

Basal hemodynamics and plasma catecholamines were measured in 10 patients with systolic hypertension, 7 males and 3 females, aged 38-69 years (Group 1), and in 10 patients with systolic and diastolic hypertension, 7 males and 3 females, aged 40-65 years (Group 2); the same measurements were repeated after acute pharmacological alpha and beta-blockade with Labetalol, 100 mg iv, or Propranolol, 10 mg iv, plus Phentolamine, 10 mg iv. In patients of Group 1 plasma noradrenaline was inversely related to systolic arterial pressure and to stroke index and was directly related to heart rate. In patients of Group 2 plasma noradrenaline was directly related to systolic arterial pressure. After acute alpha and beta-blockade the degree of reduction of systolic arterial pressure was directly related to basal plasma noradrenaline in both groups; systolic arterial pressure was reduced to normotensive levels in 5 patients of Group 1 who had high basal plasma noradrenaline values. These results confirm some of our previous findings and suggest that in some patients with systolic hypertension adrenergic activity is increased and may have a significant role in maintaining high blood pressure values.

Normocapnic anaesthesia with enflurane for intraocular surgery.

The intraocular pressure was measured by applanation tonometry in 13 patients undergoing lens extraction with normocapnic anaesthesia with 1% enflurane and controlled ventilation of the lungs with large tidal volumes (13 ml/kg). The intraocular pressure was consistently reduced by about 35% and was associated with a similar reduction in systolic arterial pressure. Provided care is taken with those patients with hypertension or heart disease who might become hypotensive, the technique is suitable for lens extraction surgery especially where it is desirable to avoid the administration of halothane.