Decrease In Peripheral Resistance Research Articles

Exaggerated systolic blood pressure response to exercise.

During aerobic exercise there is an appropriate increase in blood pressure (BP) that is primarily systolic. Aerobic exercise results in an acute increase in cardiac output as well as a decrease in peripheral resistance due to vasodilatation in the exercising muscle.1 As a result, systolic BP (SBP) rises with no change or even slight reduction in diastolic BP (DBP). Factors associated with an increase in SBP during exercise include an increase in sympathetic tone and a decrease in aortic distensibility. Exaggerated increases in SBP are often defined as a SBP >200 mm Hg during or after treadmill-based exercise or delayed return of SBP to pre-exercise levels, and they may be prognostically important. Exaggerated SBP response to exercise has been associated with an increased incidence of hypertension later in life, coronary artery disease (CAD), and left ventricular hypertrophy (LVH). In the Framingham Heart Study,2 SBP and DBP response in normotensive subjects were studied during exercise and during recovery from exercise using a graded treadmill test. An exaggerated DBP response to exercise was predictive of risk for new-onset hypertension in normotensive men and women. A prolonged recovery time for return of SBP to baseline, usually 5 minutes after completing an exercise portion, was predictive of hypertension in men. Cardiovascular mortality is increased in patients with markedly increased BP after exercise. A prospective study of 2000 apparently healthy men, aged 40 to 59 years, evaluated changes after a 6-minute standardized bicycle exercise test. The cardiovascular death rate at 16 years increased more than 2-fold in subjects with postexercise SBP >200 mm Hg.3 Two possible mechanisms include underlying LVH and increased vascular reactivity to stress. Exaggerated SBP response during exercise has also been associated with LVH. One study, however, showed that in subjects with known or suspected CAD, an exaggerated SBP response to exercise was less likely to be associated with perfusion abnormalities on thallium scan and that there was no increase in mortality at 6 years.4 A subsequent study from the same group showed a worse prognosis in patients with delayed recovery in SBP to baseline after exercise. This finding was associated with increased likelihood of severe CAD.5 Although an exaggerated SBP response to exercise has been associated with a poor prognosis and adverse CV events, the finding has not consistently been reproducible on subsequent exercise testing.6 Exaggerated increases in SBP with exercise may imply a poor prognosis although the SBP response to exercise is not always reproducible. An abnormal SBP response presents an opportunity to reinforce cardiovascular risk factor management, particularly emphasizing lifestyle measures and medication adherence. Such responses to exercise are not a contraindication, per se, to regular aerobic exercise because of the known benefits of aerobic exercise. It would be prudent, though, to recommend measuring and charting BP during and after exercise. If the patient has repeatedly elevated SBP responses during exercise, then we would consider further cardiovascular evaluation beginning with an echocardiogram for LVH and proceeding from there as directed by the individual patient characteristics.

Blood Cell Deformation in Neonates Who Have Sepsis

After completing this article, readers should be able to: 1. Describe alterations of red blood cells due to bacterial toxins. 2. Describe physical alterations of neutrophils during activation. 3. Delineate the role of red and white blood cells in the impairment of microcirculation and organ damage in sepsis. 4. List drugs that may inhibit neutrophil activation and improve their deformability and their actions. Sepsis remains a major cause of morbidity and mortality in neonates, particularly among preterm infants. (1) Impaired microcirculatory blood flow plays a pivotal role in the development of clinical manifestations and organ dysfunctions in severe sepsis and septic shock. (2)(3)(4) If not corrected, microcirculatory dysfunction can progress to organ dysfunction and subsequently to organ failure and death. Restoration of microcirculatory dysfunction is, therefore, an important step in preventing long-term sequelae (including brain damage) and death of the patient. Both red and white blood cells must deform to pass through narrow channels whose diameters are less than those of the cells. (5) Impaired deformability of red and white blood cells may contribute to impaired microcirculatory blood flow in septicemia. The membranes of neonatal red blood cells (RBCs) deform more in response to a given force than adult cells and are, therefore, more flexible. (6)(7) On the other hand, neonatal RBCs are larger and require higher pressures to enter filter pores and micropipettes that have diameters below the resting cellular diameters. (8)(9) The larger volume and increased deformability of neonatal RBCs are responsible for another favorable property, the increased Fahraeus and Fahraeus-Lindqvist effect (ie, hematocrit and viscosity reduction when going from 500- to 50-mcm tubes). (10) These favorable flow properties of neonatal RBCs suggest that their increased cellular deformability is a prerequisite for adequate flow in arterioles and capillaries. We have shown that loss of …

Blood Flow Remodels Growing Vasculature During Vascular Endothelial Growth Factor Gene Therapy and Determines Between Capillary Arterialization and Sprouting Angiogenesis

For clinically relevant proangiogenic therapy, it would be essential that the growth of the whole vascular tree is promoted. Vascular endothelial growth factor (VEGF) is well known to induce angiogenesis, but its capability to promote growth of larger vessels is controversial. We hypothesized that blood flow remodels vascular growth during VEGF gene therapy and may contribute to the growth of large vessels. Adenoviral (Ad) VEGF or LacZ control gene transfer was performed in rabbit hindlimb semimembranous muscles with or without ligation of the profound femoral artery (PFA). Contrast-enhanced ultrasound and dynamic susceptibility contrast MRI demonstrated dramatic 23- to 27-fold increases in perfusion index and a strong decrease in peripheral resistance 6 days after AdVEGF gene transfer in normal muscles. Enlargement by 20-fold, increased pericyte coverage, and decreased alkaline phosphatase and dipeptidyl peptidase IV activities suggested the transformation of capillaries toward an arterial phenotype. Increase in muscle perfusion was attenuated, and blood vessel growth was more variable, showing more sprouting angiogenesis and formation of blood lacunae after AdVEGF gene transfer in muscles with ligated PFA than in normal muscles. Three-dimensional ultrasound reconstructions and histology showed that the whole vascular tree, including large arteries and veins, was enlarged manifold by AdVEGF. Blood flow was normalized and enlarged collaterals persisted in operated limbs 14 days after AdVEGF treatment. This study shows that (1) blood flow modulates vessel growth during VEGF gene therapy and (2) VEGF overexpression promotes growth of arteries and veins and induces capillary arterialization leading to supraphysiological blood flow in target muscles.

Effect of Sildenafil on Cardiac Performance in Patients With Heart Failure

Sildenafil is rarely used in patients with heart failure despite a high prevalence of erectile dysfunction, and the theoretic possibility that by increasing nitric oxide availability, it may improve left ventricular (LV) load and performance. This study aimed to determine the peak effects of sildenafil on LV load and performance in patients with heart failure caused by systolic LV dysfunction. Twenty patients with controlled LV failure and ejection fractions <35% received sildenafil 50 mg or a matching placebo when not receiving regular medication for > or =12 hours, in a randomized, placebo-controlled, double-blind, 2-way crossover fashion. Cardiac output was measured by Doppler echocardiography. The aortic pressure waveform was determined using generalized transfer function from radial artery applanation tonometry. Aortic and femoral arterial stiffness was determined as carotid-femoral and femoral-pedal pulse-wave velocity (PWV); wave reflection was measured as an augmentation index (AIx). Cardiac index increased significantly (by 0.37 L/min.m(2), p <0.0001), with the peak effect 60 minutes after sildenafil administration. Compared with the baseline value, total systemic resistance showed a reduction of 479 dynes.s.cm(-5) (p <0.0001). Aortic and lower limb PWV decreased significantly (by 0.89 and 1.14 m/s, respectively, p <0.0001 for both), as did AIx (by 3.6% absolute, p <0.0001); these remained significant after adjustment for mean pressure and heart rate changes. In conclusion, sildenafil improves cardiac performance because of a decrease in LV load, which is caused by decreases in peripheral resistance, in aortic and large artery stiffness, and in wave reflection from peripheral sites. This can explain the increase in cardiac output and in exercise capacity with sildenafil in patients with heart failure.

Arterial stiffness and fetal growth in normotensive pregnancy

Normal pregnancy is characterized by a decrease in peripheral resistance and generalized vasodilation resulting in plasma volume expansion, which is associated with intrauterine growth. Stiffness of the arterial system may be a measure of the degree of plasma volume expansion. Pulse wave velocity (PWV), measured by applanation tonometry, is a validated approach to determine arterial stiffness. Pulse pressure (PP) is considered a surrogate measure for arterial stiffness. The aim of this study was to evaluate the association between arterial stiffness and fetal growth. In 50 normotensive pregnancies, carotid-femoral PWV was measured in the third trimester in 30 degrees lateral position. Blood pressure measurements were performed with conventional auscultatory sphygmomanometry. Birth weight centiles and weight centiles at the age of 6 months were recorded. Linear regression models were used for statistical analyses. There was a significant relationship in PWV with both birth weight centiles and catch-up growth after birth, independent of mean arterial pressure (MAP). An increase of 1 m/sec in PWV was associated with a decrease in birth weight centiles by 17.6% and a catch-up of 22.3% in weight centiles after birth. A stronger association was found for pulse pressure and birth weight centiles. An increase of 1 mm Hg was associated with a decrease in birth weight centiles by 1.8%. There was no association between MAP and birth weight centiles. In normotensive pregnancy arterial stiffness is associated with birth weight centile and catch-up growth after birth, independently from MAP. This suggests that arterial stiffness reflects maternal vascular adaptation to pregnancy better than blood pressure.

Review of clinical outcomes in nocturnal haemodialysis patients after renal transplantation.

Nocturnal haemodialysis (NHD) is a novel form of haemodialysis therapy that is associated with improved blood pressure control when compared to conventional haemodialysis (CHD). Current studies suggest that NHD lowers blood pressure through a decrease in peripheral resistance. The graft and blood pressure outcomes of NHD patients who undergo renal transplantation are unknown. We reviewed the renal allograft and blood pressure outcomes of 15 NHD patients who underwent renal transplantation. An age and vintage matched cohort of 29 CHD patients was used as controls. The rate of delayed graft function (DGF) tended to be higher in the NHD group compared to the CHD group (64 vs 41%, P = 0.15), however the 1-year graft function (53+/-6 vs 59+/-5 ml/min, P = 0.426) and graft survival (92 vs 95%, P = 0.751) were similar. Intra-operatively, NHD patients had lower minimum systolic (92+/-5 vs 109+/-4, P = 0.03) and diastolic (48+/-3 vs 64+/-2, P = 0.02) blood pressures in comparison to the CHD cohort. Pathologically, acute tubular necrosis accounted for 100% of DGF in the NHD group in contrast to 75% in the CHD population (P = 0.01). Pre-transplant mean systolic BP (sBP) was significantly lower in the NHD group compared to the CHD group (113+/-6 vs 145+/-10 mmHg, P<0.001). At 12 months post-transplant, mean sBP increased from baseline in the NHD group ( triangle up sBP 22+/-7 mmHg, P = 0.009) while in the CHD group mean sBP fell (Delta sBP -14+/-5 mmHg, P = 0.014). Mean arterial and diastolic BP exhibited similar changes. These trends persisted after 24 months of post-transplant follow-up. One-year graft outcomes and blood pressures are similar for NHD and CHD patients who undergo renal transplantation. Unlike CHD patients, NHD patients experienced a significant fall in their intra-operative blood pressures, which likely contributed towards the delayed graft function in this cohort of patients. Further prospective studies are needed to examine the underlying differences in haemodynamics and long-term graft survival between the two renal replacement modalities.

Management of older hypertensive patients: is there a difference in approach?

Hypertension is the most common reason Americans visit a physician. Recent analyses from the Framingham Heart Study and others have shown that there will be 70 million hypertensive Americans by the year 2020 and that the overwhelming majority of hypertensives will be 65 years of age or older (what we used to call elderly). The lifetime risk of Americans who live to age 85 years of becoming hypertensive is approximately 90% for both men and women. These individuals, even if they develop an elevated blood pressure late in life, are at significantly increased risk of the many medical complications attributable to hypertension (coronary artery disease, strokes, heart failure, chronic renal disease, and more). Older hypertensives are more likely to have an elevated systolic blood pressure and a low diastolic blood pressure, both of which are related to a loss of article compliance and have an increase in left ventricular mass and a decrease in peripheral resistance. We now have a substantial body of evidence from well done clinical trials that older hypertensives benefit as much or more than younger patients from antihypertensive therapy, so there is no longer any justification for withholding medication from any hypertensive patient whose competing risk or other medical problems are not a contraindication to treatment. These same studies, and practice-based analyses, have shown that the major barrier to reaching blood pressure goal is our failure to reduce systolic blood pressure to <140 mm Hg in most patients and to <130 mm Hg in diabetics and those with renal failure. The basis for all antihypertensive therapy, especially in older people, is thiazide diuretics with either angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, or calcium entry blockers as appropriate add-on treatment. The choice of the second agent depends on other factors, such as comorbidity, lifestyle, and affordability. We must be more aggressive in getting the message out that older hypertensives benefit from treatment and we must overcome the clinical inertia that seems to be a factor in the decision of many physicians not to treat an older patient. No older person should suffer a preventable, life-threatening event or become confined to a wheel chair if attention to lifestyle issues and a few pills a day could avoid that outcome.

Magnesium supplementation and deoxycorticosterone acetate--salt hypertension: effect on arterial mechanical properties and on activity of endothelin-1.

The aim of this study was to show whether the decrease in blood pressure induced by Mg supplementation in deoxycorticosterone acetate - salt (DOCA-salt) hypertensive rats is associated with mechanical modifications of blood vessels and (or) changes in tissular production and (or) vasoconstrictor activity to endothelin-1. DOCA-salt treatment increased blood pressure, media thickness, cross-sectional area, and lumen diameter of carotid arteries. Distensibility and incremental elastic modulus versus stress were not altered in carotid arteries, suggesting that the DOCA-salt vessel wall adapts structurally to preserve its blood pressure buffering capacity. Magnesium supplementation attenuated DOCA-salt hypertension. In comparison with normotensive rats, systolic, mean, and pulse pressures were higher whereas diastolic pressure was not different in Mg-supplemented DOCA-salt rats. Magnesium supplementation did not significantly modify the elastic parameters of carotid arteries. In resistance mesenteric arteries, DOCA-salt hypertension induces an inward hypertrophic remodeling. Magnesium supplementation attenuates wall hypertrophy and increases lumen diameter to the normotensive diameter, suggesting a decrease in peripheral resistance. Magnesium supplementation normalizes the altered vasoconstrictor activity of endothelin-1 in mesenteric arteries and attenuates endothelin-1 overproduction in kidney, left ventricle, and aorta of DOCA-salt rats. These findings suggest that Mg supplementation prevents blood pressure elevation by attenuating peripheral resistance and by decreasing hypertrophic effect of endothelin-1 via inhibition of endothelin-1 production.

Evaluation of cardiovascular parameters of a selenium-based antihypertensive using pulsed Doppler ultrasound.

The pharmacology of selenium is of much interest because selenium deficiency has been linked to cardiovascular diseases, cancer, and arthritis, and selenoenzymes are critical cellular antioxidants. We have previously reported that phenyl-2-aminoethylselenide (PAESe) and its derivatives represent a novel class of selenium-based antihypertensive agents that exhibit unique biochemical and pharmacologic properties. We now report on experiments designed to probe the hemodynamic mechanism of action of these compounds in spontaneously hypertensive rats (SHR). A noninvasive pulsed Doppler ultrasound probe was used to measure peak blood flow velocity in the aortic arch from the right second intercostal space. PAESe was found to increase peak aortic blood flow velocity (+44%), heart rate (+16%), and blood flow acceleration (+105%), while decreasing left ventricular ejection time (LVET) (-37%) concomitant with a decrease in mean arterial pressure (-54%). These results were compared with the known vasodilator hydralazine, which had similar effects on mean arterial pressure (MAP) and peak velocity but caused an increase in LVET (+42%) and a decrease in heart rate (-18%). Taken together, our results suggest that PAESe decreases blood pressure via a decrease in peripheral resistance, which overcomes the initial increase in heart rate and acceleration to give a net decrease in MAP.

In Vivo Canine Model Comparison of Cardiohemodynamic and Electrophysiological Effects of a New Antipsychotic Drug Aripiprazole (OPC-14597) to Haloperidol

The cardiovascular effects of aripiprazole were assessed in comparison with those of haloperidol using a halothane-anesthetized canine model with monophasic action potential monitoring. Aripiprazole (n = 6) or haloperidol (n = 6) was infused over 10 min at escalating doses of 0.03, 0.3, and 3.0 mg/kg with intervals of 20 min between doses. Clinically relevant plasma concentrations were obtained after 0.03–0.3 mg/kg of aripiprazole as well as haloperidol. After 0.03–0.3 mg/kg of aripiprazole, positive chronotropic, inotropic, and dromotropic effects, shortening of the ventricular effective refractory period (ERP) and repolarization phase, and decrease of total peripheral resistance were observed in a dose-related manner. However, in the presence of a β-blocking dose of esmolol (0.1 mg/kg/min), these changes were not induced. After 3.0 mg/kg of aripiprazole administration, cardiac effects induced by the lower doses were attenuated or disappeared, while the negative chronotropic, dromotropic, and hypotensive actions and prolongation of ERP and repolarization phase were induced. After 0.03 mg/kg of haloperidol, no significant change was observed, except for the decrease of the peripheral resistance. After 0.3–3.0 mg/kg of haloperidol, negative chronotropic, inotropic, and hypotensive actions, intraventricular conduction delay, and prolongation of ventricular ERP and repolarization phase were observed in a dose-related manner accompanied by further decrease of the peripheral resistance. The inhibitory effects of aripiprazole on cardiovascular parameters in dogs were less potent than those of haloperidol at clinically relevant exposures, moreover, aripiprazole, unlike haloperidol, neither induced early afterdepolarization nor prolonged the ventricular electrical vulnerable period. Therefore, aripiprazole can be considered safer to use than haloperidol.

Influência das Alterações Hemodinâmicas Maternas sobre o Desenvolvimento Fetal

Objetivo: avaliar as alteracoes hemodinâmicas e estruturais cardiacas maternas nos tres trimestres da gestacao e relaciona-las com a classificacao do recem-nascido, de acordo com o peso/idade gestacional. Metodos: foi realizada avaliacao ecocardiografica em 22 gestantes, sem patologias, para estudo do debito cardiaco, pressao arterial media, diâmetro do atrio esquerdo e resistencia periferica, em tres periodos da gestacao: antes da 12a , na 26a e na 36a semanas de gestacao. Dezessete gestantes deram a luz recem-nascidos com peso adequado, quatro, recem-nascidos pequenos, e uma gestante, recem-nascido grande para a idade gestacional. Resultados: nas maes que deram a luz recem-nascidos pequenos para a idade gestacional, o debito cardiaco e o diâmetro do atrio esquerdo mantiveram-se inalterados, com tendencia de elevacao da pressao arterial media e aumento de 28% da resistencia periferica, durante a gestacao. As maes que deram a luz recem-nascidos adequados para idade gestacional tiveram aumento medio do debito cardiaco de 19% entre o primeiro e segundo trimestres e de 8% entre o segundo e terceiro trimestres da gestacao. O diâmetro do atrio esquerdo elevou-se proximo de 9% durante a gestacao, com manutencao da pressao arterial media e tendencia de queda da resistencia periferica. Conclusoes: os resultados obtidos nesse trabalho suportam a associacao entre adaptacao hemodinâmica e peso do RN

Induction and maintenance of anaesthesia with sevoflurane in comparison to high dose opioid during coronary artery bypass surgery

Induction and maintenance of anaesthesia with sevoflurane in comparison to high dose opioid during coronary artery bypass surgery

Combined vascular reconstruction and free flap transfer in diabetic arterial disease.

Gangrenous lesions of the foot or lower leg due to severe diabetic arterial disease resulting in extensive soft tissue defects with exposed bones or tendons often result, even after successful revascularisation, in staged or primary amputation. We present our experience with 45 such patients treated with combined arterial reconstruction and free tissue transfer for limb-salvage. All presented with peripheral vascular disease of diabetic origin, and extensive gangrenous lesions that could not be treated by simple wound closure or skin-grafting without major amputation. A total of 53 arterial reconstructions and 47 free-flap transfers were performed. In the majority of patients, the distal anastomosis was on a pedal or tibial vessel. These bypass grafts or a native revascularized artery served as the inflow tract for the free flap which was anastomosed using microsurgical techniques. Venous anastomoses were preferentially performed on the deep venous system. Donor muscles were Musculus rectus abdominis (n=37), Musculus latissimus dorsi (n=5), Musculus serratus anterior (n=3), and a perforator flap (n=2) tailored to the size of the defect and covered with a split thickness graft (STG). The operation was set up as a combined procedure in 39/45 patients, two teams working simultaneously, limiting the mean operative time to 6 h. Early reinterventions had to be performed in 14 patients resulting in five flap losses of which two could be treated with a new free flap transfer and three were amputated. Three other patients died in the postoperative period, leaving us with a total of 39/45 patients leaving the hospital with a full-length limb. Independent ambulation was achieved in 32 of these 39 patients. During late follow-up (mean 26 months) eight bypasses occluded resulting in two amputations and two new vascular reconstructions. Combined survival and limb-salvage rate was 84% after 1 year, 77% after 2 years and 65% after 3 years. The advantages of this combined technique are: (1) it provides immediate soft tissue coverage limiting amputation level and healing time, resulting in early ambulation; (2) it provides extra run-off to the revascularisation, illustrated by a decrease in peripheral resistance, contributing to its patency; (3) the application of healthy, well vascularised tissue limits infection and enhances neovascularisation; (4) a full-length limb is preserved. We believe this combined approach offers a valuable alternative to primary amputation in this group of patients with extensive ischaemic defects.

Normal pregnancy is associated with enhanced endothelium-dependent flow-mediated vasodilation.

Normal pregnancy is characterized by reduced systemic vascular resistance, which may be mediated by nitric oxide (NO). We compared endothelial vasomotor function in 71 normal pregnant women (13 in first, 29 in middle, and 29 in last trimester) to 37 healthy age-matched controls. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia [with increased flow causing endothelium-dependent dilation (FMD)], and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with controls, resting flow and brachial artery diameter were significantly higher during the middle and last trimesters. Reactive hyperemia was reduced in all pregnant groups. FMD increased from the first trimester (by 26%), reaching the highest value in the last trimester (to 47% above nonpregnant values). FMD was significantly correlated to pregnancy status (nonpregnant or pregnant) and to vessel size. Nitroglycerin-induced dilation was similar in pregnant and nonpregnant women. A longitudinal study of eight women evaluated in the first, middle, and last trimesters confirmed an increase in FMD throughout pregnancy. The study supports the idea that basal and stimulated NO activity is enhanced in normal pregnancy and may contribute to the decrease in peripheral resistance.

Experimental treatment of the acute cardiovascular toxicity of caffeine.

The intravenous infusion of caffeine-sodium salicylate (15 mg/kg/min) into artificially ventilated and anesthetized rats caused a progressive fall in arterial blood pressure which was mainly due to a decrease in peripheral resistance. Cardiac output increased initially by 15% but then declined after 30 minutes. The electroencephalogram showed sinus tachycardia and ectopic beats mainly in the form of monomorphic ventricular bigeminy which began after 22.8 minutes. Fatal ventricular fibrillation occurred in all animals by 66.9 +/- 3.1 minutes. Treatment of cardiac arrhythmia by repeated intravenous injections of propranolol (1 mg/kg) or verapamil (1 mg/kg) was effective and prolonged survival time to 91.7 +/- 4.4 or 84.3 +/- 2.9 minutes, respectively (p < 0.05). Propranolol also prolonged survival time when administered in a single dose of 20 mg/kg i.v. 10 minutes before the initiation of caffeine infusions. Repeated administrations of quinidine sulfate (5 mg/kg), phenytoin (5 mg/kg), or lidocaine (1-5 mg/kg), on the other hand, exerted very short antiarrhythmic activity and did not prolong survival time at all. Fluid therapy with polygeline plasma expander (0.5 mL/kg/min) did not influence caffeine-induced cardiovascular failure in any way. Ventricular ectopia leading to fibrillation accounts for the lethal outcome of caffeine poisoning in anesthetized rats and can be antagonized by treatment with propranolol or verapamil.

Renal response to hemodilution with albumin or crosslinked bovine hemoglobin: Role of nitric oxide

The decreased hematocrit that occurs with hemodilution leads to a decrease in peripheral resistance while venous return and cardiac output increase. We determined systemic and renal responses to hemodilution with a solution of albumin or a crosslinked hemoglobin-based oxygen carrier (XLHb) and the effect of inhibition of NO synthesis on the responses to albumin. Clearance experiments were done on anesthetized rats to determine mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and sodium excretion before and after isovolemic exchange transfusion (2 ml per 100 gm body weight) with either (1) 5% albumin (n = 5), (2) 5% albumin plus Nω-nitro-L-arginine methyl ester (L-NAME, 3.5 mg/kg; n = 6), or (3) 6% XLHb (n = 7) and after administration of L-NAME alone (n = 4). Hematocrit decreased similarly in all exchange groups (from 42 ± 1.0 to 29 ± 1.3). MAP decreased with albumin exchange, increased with LNAME, and remained unchanged with albumin+L-NAME or XLHb. GFR, ERPF, and renal blood flow increased while filtration fraction and renal resistance decreased with albumin exchange; responses were the opposite with L-NAME, and with albumin+L-NAME and XLHb these parameters remained approximately the same as control values. Red cell delivery decreased with L-NAME, albumin+L-NAME, and XLHb but remained at control levels with albumin. In conclusion, renal effects of decreased hematocrit can be offset by decreased NO availability. The similarity of results with XLHb and albumin+L-NAME is consistent with NO scavenging by hemoglobin. Increased renal vascular tone with XLHb limits oxygen delivery.

Cardiovascular Function Before, During, and After the First and Subsequent Pregnancies

This study was designed to test the hypothesis that the vascular remodeling of pregnancy begins early, persists for at least 1 year after delivery, and is accentuated by a second pregnancy. Serial estimates of heart rate, arterial pressure, left ventricular volumes, cardiac output, and calculated peripheral resistance were obtained before pregnancy, every 8 weeks during pregnancy, and 12, 24, and 52 weeks postpartum in 15 nulliparous and 15 parous women using electrocardiography, automated manometry, and M-mode ultrasound. During pregnancy, body weight increased 14.5 ± 1.8 kg and returned to prepregnancy values 1 year postpartum. Heart rate peaked at term 15 ± 1 beat/min above prepregnancy levels (57 ± 1 beat/min). Mean arterial pressure reached its nadir (−6 ± 1 mm Hg) at 16 weeks, returning to baseline at term. The increases in left ventricular volumes and cardiac output (2.2 ± 0.2 L/min) peaked at 24 weeks as did the 500 ± 29 dynes·cm·s −5 decrease in peripheral resistance, and their magnitude was significantly greater in the parous women. Postpartum they gradually returned toward baseline but remained significantly different from prepregnancy values in both groups at 1 year. We conclude that cardiovascular adaptations to the initial pregnancy begin early, persist postpartum, and appear to be enhanced by a subsequent pregnancy. We speculate that persistence of these changes may lower cardiovascular risk in later life.

Control of tissue blood flow at very low temperatures

Maximum levels of sustainable swimming activity rely on aerobic metabolism, and hence are limited by the cardiovascular supply capacity which is impaired at low temperatures. It is unclear to what extent species adapted to a continuous cold environment retain control of regional blood flow. Muscle blood flow (MBF) was therefore measured using the radiolabelled microsphere method in the Antarctic teleost Notothenia coriiceps and compared with data for trout at their preferred (optimal) temperatures of 0°C and 11°C, respectively. In resting fish, blood flow distribution to skeletal muscle was similar (around 8 ml/min/100 g), despite a lower cardiac output in Notothenia (7 vs. 27 ml/min). Following maximal exercise there was a significant increase in specific blood flow to slow, but not fast, muscle in both species. However, the relative hyperaemia was greater in trout (6.6- vs. 9.3-fold, respectively), with a similar relative increase in cardiac output (2.3- vs. 3.4-fold, respectively). The increase in blood flow to slow muscle, and decrease in peripheral resistance, during maximal exercise in trout (and hence regional O 2 delivery by convective transport) appears to be determined centrally. In contrast, reduced active redistribution from the viscera in Notothenia is presumably responsible for the attenuated increase in MBF on exercise. However, regional hyper- and hypoperfusion can occur within a single locomotory muscle, suggesting control of vascular tone is maintained.

Effects of hypervolemia on interdialytic hemodynamics and blood pressure control in hemodialysis patients

The influence of hypervolemia on hemodynamics and interdialytic blood pressure, as well as in relation to vascular compliance, was investigated in 10 hemodialysis patients who were not receiving vasoactive medication. All subjects were studied during a relative normovolemic interdialytic period (from 1 kg below dry weight postdialytic until dry weight predialytic) and a hypervolemic interdialytic period (from 1 kg above dry weight postdialytic until 3 kg above dry weight predialytic). Interdialytic blood pressure was measured with an ambulatory blood pressure monitor. Cardiac output was echographically measured and total peripheral resistance calculated postdialytic, mid-interdialytic, and predialytic. At the same time, a blood sample was drawn for analyzing vasoactive hormones, sodium, and hematocrit. In all patients, ideal dry weight was estimated by echography of the caval vein. Arterial and venous compliance were measured with an ultrasound vessel wall movement detector system and a strain-gauge plethysmograph. After fluid load, an increase in intravascular volume, an increase in caval vein diameter and cardiac output, and a decrease in peripheral resistance was observed. No significant influence of a 3-L fluid load was found on interdialytic blood pressure course (153 ± 24 mm Hg/90 ± 19 mm Hg in the hypervolemic period and 146 ± 27 mm Hg/89 ± 22 mm Hg in the normovolemic period). Sodium and osmolality were similar in the hypervolemic and normovolemic interdialytic periods. After fluid load, a decrease in arginine vasopressin and angiotensin II was observed, which probably contributed to the decreased systemic vascular resistance. Catecholamines were not influenced by fluid load, but increased during the interdialytic period, suggesting accumulation after dialysis. Three of the 10 patients had higher systolic but not diastolic blood pressures after fluid load (159 ± 13 mm Hg/81 ± 22 mm Hg in the hypervolemic period and 135 ± 16 mm Hg/81 ± 22 mm Hg in the normovolemic period). No correlation could be found between arterial or venous compliance and blood pressure changes. We concluded that a 3-L interdialytic fluid load does not result in higher blood pressure in most hemodialysis patients.

The influence of pregnancy on endothelium-derived nitric oxide mediated relaxations in isolated human resistance vessels.

Pregnancy is associated with drastic hemodynamic adaptations, including a decrease in peripheral resistance. Vascular resistance is substantially influenced by endothelium-derived nitric oxide (NO). This study was designed to investigate whether pregnancy might influence endothelium-derived NO-mediated relaxations in human resistance arteries. Reactivity of isolated human subcutaneous arteries, dissected out of abdominal fat from women who underwent a laparotomy or cesarean section, was studied using a small vessel myograph. Addition of acetylcholine (1 nM-10 microM) or bradykinin (1 nM-10 microM) to precontracted preparations elicited concentration-dependent relaxation responses that were dependent on the presence of the endothelium and were partially inhibited by the NO-synthase inhibitor nitro-L-arginine (0.1 mM). The relaxations to acetylcholine and bradykinin were similar in vessels isolated from pregnant and non-pregnant women. Nitro-L-arginine (0.1 mM) had no influence on basal tone and had a similar inhibitory influence on the endothelium-mediated relaxations in vessels from non-pregnant and pregnant women. These results indicate that the influence of endothelium-derived NO in human subcutaneous resistance arteries is not altered at the end of pregnancy.