Lower Mean Blood Pressure Research Articles

Preterm Circulatory Support Is More Complex Than Just Blood Pressure

To the Editor .— We agree with Munro et al1 that adequate cerebral blood flow (CBF) is important to protecting the preterm brain, but we disagree that this can be ensured solely on the basis of a mean blood pressure (MBP) of >30 mm Hg. Our studies show a period of vulnerability to low systemic blood flow (SBF) within the first 12 hours; it affects all organs (not just the brain), it is not always shown by low MBP, and it relates strongly to adverse neurologic outcome.2,3 Age of the infant (even within the first 40 hours) is critical …

Persistent Sympathetic Activation During Chronic Antihypertensive Therapy

Previous studies have demonstrated that antihypertensive treatment resets baroreflex control of heart rate (HR) and increases cardiac vagal baroreflex sensitivity. However, it is uncertain whether baroreflex control of muscle sympathetic nerve activity (MSNA) also resets after treatment. We tested the hypothesis that chronic antihypertensive therapy alters baroreflex regulation of MSNA in patients with untreated moderate hypertension. Seven newly diagnosed patients with systolic blood pressure (BP) of 159+/-5 mm Hg (mean+/-SE) and diastolic BP of 103+/-4 mm Hg were studied before and after 1 to 2 weeks ' and 3 months (chronic) of antihypertensive treatment with losartan-hydrochlorothiazide (Hyzaar). MSNA and hemodynamics were measured supine, during a Valsalva maneuver (VM), and at 70 degrees head-up tilt (HUT) for 10 minutes. Data were compared with those obtained in 7 age-matched healthy controls. We found that Hyzaar lowered mean BP acutely and chronically by 20+/-4 and 23+/-3 mm Hg (both P<0.01) but did not change HR. Supine MSNA increased by 43+/-11% and 34+/-11% after acute and chronic treatment (both P<0.01). However, MSNA responses to VM and HUT did not differ after treatment compared with before treatment, indicating unchanged reflex control. These data indicate that sympathetic neural activity was augmented substantially by antihypertensive treatment with Hyzaar, consistent with an ongoing baroreflex unloading, and did not return to baseline or "reset" after 3 months of therapy. We speculate that persistent and marked sympathetic activation by the baroreflex may be a potential mechanism for hypertension that is refractory to antihypertensive therapy and may provide a target mechanism for persistent morbidity despite adequate BP control.

PANAX NOTOGINSENG SUPPLEMENTATION ENHANCES PHYSICAL PERFORMANCE DURING ENDURANCE EXERCISE&lt;//i&gt;

The purpose of this study was to investigate whether a single 1,350-mg dose of Panax notoginseng (PNG) could enhance aerobic capacity, endurance, and mean blood pressure (MAP) in young adults. We randomly assigned 29 untrained adults, aged 20-35 years, to an experimental (EXP, n = 13) or a control (CON, n = 16) group. For 30 days, the EXP took 1,350 mg per day of PNG capsule and the CON consumed 1,350 mg per day of starch capsule. Measurement variables were taken before and after 30 days of either PNG supplement or placebo. Results show that the EXP improved (p < 0.05) their endurance time by >7 minutes, and lowered (p < 0.05) maximal MAP (from 113 +/- 12 to 109 +/- 14 mm Hg) and Vo2 at the 24th minute (from 32.5 +/- 8 to 27.6 +/- 8 ml.kg-1.min-1) during endurance cycle exercise. Based on this study, we conclude that 1,350 mg per day PNG supplement for 30 days improved endurance time to exhaustion, and lowered MAP and Vo2 during endurance exercise.

Breast-feeding has little effect on blood pressure in later life*1

Is breast feeding, compared with bottle feeding with formula milk, associated with lower mean blood pressure in later life? Systematic review with meta-analysis. Twenty four studies were identified (12 cross-sectional studies, 11 cohort studies and one randomised controlled trial). Average systolic blood pressure was significantly lower in people who were breast fed as an infant compared with infants that were bottle fed (−1.10 mmHg, 95% CI -1.78 to -0.42 mmHg). There was no significant difference in diastolic blood pressure between feeding groups. However, there was significant heterogeneity across studies (see Notes), so these results should be interpreted with caution. Breast feeding in infancy has at best, a modest effect on systolic blood pressure in later life compared with bottle feeding.

Breast-feeding has little effect on blood pressure in later life

Question Is breast feeding, compared with bottle feeding with formula milk, associated with lower mean blood pressure in later life? Study design Systematic review with meta-analysis. Main results Twenty four studies were identified (12 cross-sectional studies, 11 cohort studies and one randomised controlled trial). Average systolic blood pressure was significantly lower in people who were breast fed as an infant compared with infants that were bottle fed (−1.10 mmHg, 95% CI -1.78 to -0.42 mmHg). There was no significant difference in diastolic blood pressure between feeding groups. However, there was significant heterogeneity across studies (see Notes), so these results should be interpreted with caution. Authors’ conclusions Breast feeding in infancy has at best, a modest effect on systolic blood pressure in later life compared with bottle feeding.

Gender Differences in Biobehavioral Aftereffects of Stress on Eating, Frustration, and Cardiovascular Responses1

Eating, persistence, and cardiovascular responses were evaluated after exposure to a 25‐min noise stressor with or without perceived control. Participants were healthy men (n = 29) and women (n = 34), aged 21 to 45 years. There were no group differences in cognitive task performance or blood pressure during the stressor. However, perceived control resulted in lower mean blood pressure and heart rate after cessation of the stressor for men and women. Women without perceived control displayed greater frustration levels following the stressor, and frustrated women ate more bland food than did nonfrustrated women. Perceived control and frustration did not affect food consumption among men following the stressor. These findings indicate that there are health‐relevant gender differences in biobehavioral responses that occur in the aftermath of stressor exposure. In addition, perceived control was especially important for women to attenuate the behavioral and biological effects of stressor exposure.

Plasma endothelin-1 and clinical manifestations of neonatal sepsis

To determine whether plasma endothelin-1 (ET-1) relates to clinical manifestations of sepsis in the newborn, especially with systemic hypotension, acidosis, severe hypoxemia (which may represent pulmonary hypertension) and oliguria. Prospective study of 35 consecutive newborns with clinical sepsis: 22 with hemoculture-positive (HC+) sepsis and 13 hemoculture-negative (HC-). Plasma ET-1 concentrations were measured within 2 days of the diagnosis of sepsis. SNAP-II severity score was performed at the time of highest clinical severity. Newborns with HC+ sepsis had higher plasma ET-1 concentrations and SNAP-II scores (especially PO 2 /FiO 2 ratio) than HC- septic children. Plasma ET-1 concentrations increased linearly with each item of the SNAP-II score, but only reached significant differences in lowest mean blood pressure (P=0.030), lowest pH (P=0.048), multiple seizures (P=0.010) and lowest urine output (P=0.013). Leukocyte count, immature/total neutrophil ratio and C-reactive protein value were not different. Each item of the SNAP-II score was independently related only to ET-1 level. Oliguria, acidosis and systemic hypotension were more correlated (R 2 >0.5). Plasma ET-1 levels in neonatal sepsis are related to the severity of clinical manifestations, especially oliguria, acidosis and systemic hypotension.

The role of blood pressure variability in end-organ damage.

The ultimate goal when treating high blood pressure is to reduce the incidence of end-organ damage and prevent cardiovascular disease, and thus reduce the incidence of premature death. Cuff blood pressure measurements have some prognostic value and have traditionally been used to predict the risk of end-organ damage. Such measurements, however, do not reflect accurately the 24-h mean blood pressure and hourly variations. For any value of cuff blood pressure, a lower 24-h mean blood pressure was associated with a lower prevalence and severity of end-organ damage. In the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, data from 24-h ambulatory blood pressure monitoring (ABPM) were more strongly associated with prognosis than other blood pressure data. Longitudinal evidence of the clinical relevance of 24-h ABPM data in predicting cardiovascular risk is less extensive. However, results from the Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation (SAMPLE) trial show the superiority of mean 24-h, daytime and night-time blood pressures over clinic readings in predicting the regression of left ventricular mass index in treated hypertensive patients. Furthermore, a direct, positive relationship has been established between 24-h blood pressure variability and the severity and rate of progression of end-organ damage. In addition, ABPM data demonstrate that hypertensive patients who do not exhibit a nocturnal reduction in blood pressure have a higher incidence of end-organ damage. Future directions for research and treatment of hypertension will need to consider the circadian cycle of blood pressure, the effect of treatment on blood pressure variability, and the magnitude of blood pressure changes in daily life.

Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial

Objective: To determine whether supplementation of infant formula milk with long chain polyunsaturated fatty acids (LCPUFAs) influences blood pressure in later childhood.Design: Follow up of a multicentre, randomised controlled trial.Setting:...

Angiographical severity of coronary atherosclerosis predicts death in the first year of hemodialysis.

Cardiac deaths and events tend to cluster within the early-phase after starting dialysis. Our goal is to clarify the influence of severity of coronary atherosclerosis on early-phase death after starting hemodialysis (HD) therapy. Eighty-three consecutive patients [mean age 62 years; male/female 64/19; diabetic nephropathy in 50 (54%)] with end-stage renal disease who admitted to our hospital to initiate regular HD treatment, and then received coronary angiography within 3 months after first dialysis therapy, were eligible for this study. Angiographical severity of coronary atherosclerosis was scored by numerically using Gensini scoring system. The patients who died within one year from starting HD were compared with those who survived as control by means of logistic regression analysis. Of 83 patients, 12 (14%) died less than one year after starting dialysis therapy. Of these 12 patients, nine died for cardiac causes. Confirmed predictors of death from cardiac cause were older age (>70 years), lower mean blood pressure (<100 mmHg), presence of ischemic heart disease (IHD), myocardial infarction (MI), angina pectoris (AP), chronic heart failure (CHF), poor cardiac function, abnormal wall motion of left ventricule (LV) and angiographical severity of coronary atherosclerosis by univariate model. Adjusting for confounding variables by multivariate model, only severity of coronary atherosclerosis (Gensini score >40 points) had a powerful influence, increasing risk for cardiac cause of early-phase death by about 17 times. Severity of coronary atherosclerosis predicts death in the first year of HD. These findings suggest that the strategy for prevention of coronary atherosclerosis should be instituted during the early phase of chronic renal failure.

Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension.

Endothelin (ET)-1 contributes to raising blood pressure (BP) and inducing cardiovascular disease by vasoconstriction and potent stimulation of aldosterone secretion. In the rat this latter effect occurs via ET(B) receptors; in humans in vitro studies implicated both ET(A) and ET(B) receptors, but there is no conclusive evidence in vivo. We recruited 13 consenting hypertensive patients: six with primary aldosteronism (PA) and seven with high-to-normal renin hypertension (HNRH). They were infused with a low dose (200 nmol/min for 5 min followed by 100 nmol/min for 10 min) of the ET(A)-selective antagonist BQ-123 either alone or, on a different day, together with an identical dose of the ET(B)-selective antagonist BQ-788. Plasma aldosterone, cortisol and ACTH concentration and plasma renin activity (PRA) were measured with radioimmunoassay at -15, 0, 30, 60, 120, 240, 360 min, while BP was recorded non-invasively. BQ-123 alone and combined with BQ-788 significantly lowered mean BP in both PA and HNRH patients (by 6-10 mmHg at nadir; P<0.01). In PA patients, a short-lived decrease of aldosterone was elicited by combined BQ-123 and BQ-788 (-14%; P<0.05), but not by BQ-123 alone; cortisol, ACTH, and PRA were unaffected by either treatment. In HNRH patients, BQ-123 both alone and combined with BQ-788 lowered aldosterone (-39 and -28%, respectively) and PRA (-43 and -16%, respectively), while cortisol and ACTH were unaffected. Endogenous ET-1 contributes to maintaining the high BP values and the aldosterone secretion in both PA and HNRH patients. In the former patients, the aldosterone secretagogue effect of ET-1 is mediated via ET(B) receptors, while in the latter it occurs mainly via ET(A)-mediated stimulation of renin production.

Hypertension as a determinant of survival for patients treated with home dialysis

Previous studies of the risks of hypertension for dialysis patients have yielded conflicting results. The aim of this study was to investigate, in a home dialysis population with low rates of diabetes and antihypertensive drug use, whether blood pressure (BP) was an independent risk factor for survival. The outcome of 168 consecutive patients (94 male, 88% Caucasian), aged 48 years (SD 16), who began home hemodialysis (HD; N = 124) or home continuous ambulatory peritoneal dialysis (CAPD; N = 44) between January 1, 1985 and December 31, 1994 were analyzed retrospectively. Only 4.7% of patients took antihypertensive drugs while on dialysis. The patients were followed to December 31, 1998 with the primary outcome being all-cause mortality. Censoring events were transplantation, transfer to another center and treatment modality change. The Cox proportional hazard model was used with baseline predictors. Seventy-one patients died and the median overall survival was 4.2 years (5.6 on HD, 2.2 on CAPD, P < 0.0001). Mean BP at start of dialysis predicted survival on its own (P = 0.0009) and in the joint Cox model (P = 0.047). Other significant predictors in the joint model were age [10 year increase, relative hazard (RH) = 1.55, P = 0.0008], albumin (10 g/L decrease, RH = 2.05, P = 0.007), diabetes (RH = 3.42, P = 0.015) and peripheral vascular disease (RH = 2.19, P = 0.02) but not dialysis modality (RH = 1.63, P = 0.13). High and low mean blood pressure (BP) values at the start of dialysis were associated with the highest mortality. Among the home dialysis patients, most of whom did not require antihypertensive drugs, hypertension was a risk factor for survival and patients with mid-range BP values survived the longest.

Cardiovascular remodeling is greater in isolated systolic hypertension than in diastolic hypertension in older adults: the Insufficienza Cardiaca negli Anziani Residenti (ICARE) a Dicomano Study

ObjectivesWe investigated cardiac and vascular remodeling in an unselected older population with either diastolic hypertension (HTN) or isolated systolic hypertension (ISH). BackgroundIsolated systolic hypertension accounts for a substantial proportion of hypertension in individuals older than 65 years and is strongly associated with an increased risk of cardiac and cerebrovascular events. The exact mechanisms underlying the increased risk associated with ISH and elevated pulse pressure (PP), in comparison with HTN, have not been extensively investigated. MethodsCommunity-dwelling residents age ≥65 years in a small town in Italy (Dicomano) were enrolled. Untreated subjects considered in this study included 173 normotensive subjects (blood pressure [BP] <140/90 mm Hg), 95 subjects with HTN (diastolic BP ≥90 mm Hg), and 43 subjects with ISH (BP ≥160/<90 mm Hg). All subjects underwent extensive clinical examination, echocardiography, carotid ultrasonography, and carotid applanation tonometry. ResultsSubjects with ISH had higher left ventricular (LV) mass, which was independently related to PP but not to systolic or mean pressures. Both carotid wall cross-sectional area and vascular stiffness were greater in ISH patients than in HTN and normal subjects and were independently related to PP but not to systolic BP. In addition, ISH was associated with a higher prevalence of carotid plaque and more extensive carotid atherosclerosis. ConclusionsIn our community-based elderly population, individuals with ISH had higher prevalences of LV hypertrophy and carotid atherosclerosis than subjects with HTN despite lower mean BP. These findings provide potential pathophysiologic mechanisms underlying the associations of ISH and PP with increased risk of cardiovascular morbidity and mortality.

Impaired urinary cortisol excretion and early cardiopulmonary dysfunction in immature baboons.

Early adrenal insufficiency is associated with cardiopulmonary dysfunction in immature infants. Isolated cortisol levels and ACTH stimulation testing may not adequately show ontogeny of postnatal cortisol secretion nor identify at risk infants. Our objectives were 1) to determine postnatal urinary cortisol excretion rate (UCER) from birth to 14 d in immature baboons and 2) to evaluate the relation between UCER and cardiac performance. UCER was assessed via 6-h blocked urine collections from birth to 336 h of age in twenty-one 125-d gestation (term = 185 d) baboons. Urinary cortisol was measured by RIA. Cardiopulmonary parameters were averaged over the same time periods as urine collection. Serial two-dimensional echocardiograms were performed. After 24-h age, a subgroup (n = 8) received up to four doses (0.5-1.0 mg/kg each) of hydrocortisone for refractory hypotension. UCER significantly increased from 0 to 6 h through 66 to 72 h age for non-cortisol-treated infants. Significantly reduced UCER patterns between birth and 24 h were found for animals subsequently requiring cortisol treatment. Cortisol-treated infants had lower mean blood pressure, worse metabolic acidosis, increased fluid needs, and impaired left ventricular function between 12 and 48 h of age. No group differences were found in gas exchange or ventilator support. We conclude that adrenal cortisol secretion significantly improves over the initial 72 h of life in the 125-d immature baboon. Failure to increase UCER after 12-24 h of life correlated with poor cardiovascular function that improved with hydrocortisone therapy. Adrenal hypofunction in the immature baboon is similar to the very preterm human and could serve as a model for future postnatal investigations.

Exercise training in obesity lowers blood pressure independent of weight change.

We used the rabbit model of obesity and exercise training to determine effects of exercise training during the development of obesity on resting blood pressure and heart rate, ventricular hypertrophy, blood volume, and hormonal profile. Female New Zealand white rabbits were assigned to one of four groups: lean sedentary (L-S, N = 17), lean exercise-trained (L-EX, N = 16), obese sedentary (O-S, N = 18), and obese exercise-trained (O-EX, N = 15). Lean rabbits were fed a maintenance diet whereas obese rabbits were fed an ad libitum high fat (10% added fat) diet. Simultaneously, exercise-trained animals underwent a progressive treadmill exercise training protocol for 12 wk. After 12 wk of diet and exercise regimens, resting blood pressure and heart rate were measured from a central ear artery catheter. Ventricular hypertrophy was evaluated using wet ventricular weights. Blood volume was measured using the Evans blue dye procedure; hormonal profile was evaluated from arterial plasma/serum samples. After 12 wk, O-S and O-EX had similar body weights and similar percentage increases in body weight. Despite similar body weights, O-EX had an approximate 6-mm Hg lower mean blood pressure compared with the elevated pressure seen in O-S (P < or = 0.05). Obese rabbits had greater resting heart rate, plasma cholesterol and triglycerides, and plasma renin activity compared with lean rabbits, and these values were unaffected by exercise training. Plasma and blood volumes, as well as plasma insulin, cortisol, and aldosterone were unaffected by exercise training. These data suggest that exercise training, in the absence of differences in body weight, may be useful in the reduction of obesity-induced hypertension but that other therapies may be needed in order to control other cardiovascular risk factors.

Exercise training in obesity lowers blood pressure independent of weight change

CARROLL, J. F., and C. K. KYSER. Exercise training in obesity lowers blood pressure independent of weight change. Med. Sci. Sports Exerc., Vol. 34, No. 4, pp. 596–601, 2002. Purpose We used the rabbit model of obesity and exercise training to determine effects of exercise training during the development of obesity on resting blood pressure and heart rate, ventricular hypertrophy, blood volume, and hormonal profile. Methods Female New Zealand white rabbits were assigned to one of four groups: lean sedentary (L-S, N = 17), lean exercise-trained (L-EX, N = 16), obese sedentary (O-S, N = 18), and obese exercise-trained (O-EX, N = 15). Lean rabbits were fed a maintenance diet whereas obese rabbits were fed an ad libitum high fat (10% added fat) diet. Simultaneously, exercise-trained animals underwent a progressive treadmill exercise training protocol for 12 wk. After 12 wk of diet and exercise regimens, resting blood pressure and heart rate were measured from a central ear artery catheter. Ventricular hypertrophy was evaluated using wet ventricular weights. Blood volume was measured using the Evans blue dye procedure; hormonal profile was evaluated from arterial plasma/serum samples. Results After 12 wk, O-S and O-EX had similar body weights and similar percentage increases in body weight. Despite similar body weights, O-EX had an approximate 6-mm Hg lower mean blood pressure compared with the elevated pressure seen in O-S (P ≤ 0.05). Obese rabbits had greater resting heart rate, plasma cholesterol and triglycerides, and plasma renin activity compared with lean rabbits, and these values were unaffected by exercise training. Plasma and blood volumes, as well as plasma insulin, cortisol, and aldosterone were unaffected by exercise training. Conclusion These data suggest that exercise training, in the absence of differences in body weight, may be useful in the reduction of obesity-induced hypertension but that other therapies may be needed in order to control other cardiovascular risk factors.

Commuting, leisure-time physical activity, and cardiovascular risk factors in China.

The relationship between both commuting and leisure-time physical activity and selected cardiovascular risk factors was analyzed. A cross-sectional survey was carried out in 1996 in urban Tianjin, China. A total of 2002 male and 1974 female subjects aged 15-69 yr completed the survey. Commuting, leisure-time physical activity, body mass index, blood pressure, and cigarette smoking were determined. Doing more than 60 min of commuting physical activity or combined commuting and leisure-time physical activity was related to the highest mean blood pressure and the highest prevalence of hypertension among both genders compared with going to and from work by bus; 31-60 min commuting only or commuting plus leisure-time physical activity was associated with the lowest mean blood pressure in women and the lowest prevalence of hypertension in both genders. Daily time on commuting or leisure-time physical activity was inversely related to mean body mass index and prevalence of overweight among men and prevalence of smoking among both genders. The present study suggests that commuting and leisure-time physical activity were favorably associated with cardiovascular risk factors in this Chinese population, except that more than 60 min of physical activity was associated with high blood pressure.

Cyclooxygenase-2 inhibitors attenuate increased blood pressure in renovascular hypertensive models, but not in deoxycorticosterone-salt hypertension.

COX-2 is an inducible cyclooxygenase (COX) that has been reported to be expressed in the macula densa and surrounding cortical thick ascending limb in normotensive rats. The present study assessed the contribution of COX-2 in three different rat models of hypertension, each characterized by a different activation of the renal renin-angiotensin system. Mean blood pressure (MBP) in the rat 2 kidney-1 clip (2K1C) model was significantly reduced with a COX-2 selective inhibitor, NS-398 (10 mg/kg, p.o., twice a day) (vehicle-administered rats (n = 8): 154 +/- 6 mmHg; NS-398-administered rats (n = 5): 128 +/- 10 mmHg). By contrast, a COX-1 selective inhibitor, mofezolac, did not lower MBP. Increased plasma renin activity (23 +/- 8 ng/kg/h (n = 6) vs. sham operation, 2.4 +/- 0.9 ng/kg/h (n = 4)) was markedly reduced to 6.8 +/- 2.7 ng/ml/h (n = 5) by NS-398, but not by mofezolac. The development of 1 kidney-1 clip (1K1C) hypertension was also inhibited by NS-398 (vehicle (n = 12): 133 +/- 1 mmHg; NS-398 (n = 7): 122 +/- 3 mmHg) accompanied by a reduction in plasma renin activity (3.0 +/- 0.3 ng/ml/h, n = 4) to 1.0 +/- 0.2 ng/ml/h (n = 5). The COX-2 inhibitor increased urinary excretions in the 1K1C model, but not in the 2K1C model. In a deoxycorticosterone acetate (DOCA)-salt model, plasma renin activity was markedly suppressed to less than 0.3 ng/ml/h. The COX-2 inhibitor caused no significant changes in MBP, plasma renin activity, or urinary excretion, suggesting that COX-2 made a lesser contribution in this model. Increased expression of COX-2 mRNA and protein was observed in the kidneys of 1K1C and 2K1C rats, but not in DOCA-salt rats. These results suggest that COX-2 plays a significant role in the development of 2K1C and 1K1C renovascular hypertension, in addition to making a substantial contribution to the diuretic effect in the 1K1C model.

The Impact of Ischaemic Preconditioning on Spinal Cord Blood Flow and Paraplegia

Purpose: We investigated the effect of ischaemic preconditioning (IP) on ischaemic spinal cord injury in a rabbit model. Methods: Fourteen rabbits were divided into IP and control groups of seven rabbits each. We repeated 3-min clamping of the infrarenal abdominal aorta and 3-min reperfusion twice (preconditioning), followed by 15 min clamping in the IP group. In the control group, the aorta was clamped for 15 min without preconditioning. Lumbar cord blood flow and systemic blood pressure were measured until 3 h of reperfusion. Another 14 rabbits underwent the same procedures with or without IP and neurologic status was assessed on the second postoperative day. Results: The percent change in lumbar cord blood flow after reperfusion was significantly greater ( P = 0.013) in the IP group despite lower mean blood pressure. There was no significant difference in overall neurologic status ( P = 0.461) but the incidence of spastic paraplegia in the IP group was lower (14%. 1/7) than that of control group (43%. 3/7). Conclusion: IP increased postischaemic lumbar cord blood flow and contributed to lower incidence of spastic paraplegia.

Effect of ABT‐627 (A‐147627), a potent selective ETA receptor antagonist, on the cardiopulmonary profile of newborn lambs with surgically‐induced diaphragmatic hernia

1. Postnatal mortality in isolated congenital diaphragmatic hernia (CDH) is mainly related to the associated pulmonary hypertension (PH) and to right-to-left shunting. 2. Endothelins (ETs) are potent vasoconstrictors and pro-mitogenic peptides. Strong evidences support their participation in CDH and in the etiology of PH via the activation of ET(A) receptors (ET(A)-Rs). 3. Evaluation of the effect of ABT-627, a selective non-peptidic ET(A)-R antagonist, given from -15 to 210 min post-delivery (1 mg kg(-1) bolus +0.01 mg kg(-1) h(-1) infusion, i.v.), was conducted in the lamb model of CDH. 4. Severity of CDH was assessed in comparison to untreated controls (n=5). Untreated CDH lambs (n=7) had a higher mean pulmonary arterial pressure (MPAP; P<0.0001), lower mean blood pressure (MBP; P=0.0004), higher MPAP / MBP ratio (P<0.0001), lower arterial pH (P<0.0001), higher paCO(2) (P<0.0001), lower paO(2) (P<0.0001) and lower post-ductal pulsatile SaO(2) (P<0.0001) than untreated controls. 5. Treated controls (n=7) showed a higher MPAP, lower MBP, higher MPAP/MBP ratio, lower arterial pH, higher paCO(2), lower paO(2), lower post-ductal pulsatile SaO(2) and lower plasmatic ir-ET ratios compared to untreated controls (P<0.0001). 6. Treated CDH lambs (n=8) showed a higher MBP (P<0.0001), lower MPAP / MBP ratio (P<0.0001), higher arterial pH (P<0.0001), lower paCO(2) (P<0.0001), higher paO(2) (P=0.0228), higher post-ductal pulsatile SaO(2) (P=0.0016) and lower plasmatic ir-ET ratios (P=0.0247) when compared to untreated CDH lambs. 7. These observations revealed that, although acute perinatal treatment with a selective non-peptidic ET(A)-R antagonist had some adverse effects in controls, it attenuated the progressive cardiopulmonary deterioration that occurred after birth in CDH lambs.