Decrease In Peripheral Resistance Research Articles

Experimental Protocol for Cecal Ligation and Puncture Model of Polymicrobial Sepsis and Assessment of Vascular Functions in Mice.

Sepsis is the systemic inflammatory response syndrome that occurs during infection and is exacerbated by the inappropriate immune response encountered by the affected individual. Despite extensive research, sepsis in humans is one of the biggest challenges for clinicians. The high mortality rate in sepsis is primarily due to hypoperfusion-induced multiorgan dysfunctions , resulting from a marked decrease in peripheral resistance. Vascular dysfunctions are further aggravated by sepsis-induced impairment in myocardial contractility. Circulatory failure in sepsis is characterized by refractory hypotension and vascular hyporeactivity (vasoplegia) to clinically used vasoconstrictors. To investigate the complex pathophysiology of sepsis and its associated multiple organ dysfunction, several animal models have been developed. However, cecal ligation and puncture (CLP) model of murine sepsis is still considered as 'gold standard' in sepsis research. In this protocol we have described the standard surgical procedure to induce polymicrobial sepsis by cecal ligation and puncture. Further, we have described the protocol to study the molecular mechanisms underlying vascular dysfunctions in sepsis.

DIMEPHOSPHON EFFECTS ON SKIN MICROHAEMODYNAMICS

Aim . To demonstrate basic mechanisms of dimephosphon operation on skin microhaemodynamics. Materials and methods. The study of dimephosphon effect on blood microcirculation of skin in outbred male rats included registration of perfusion index, mean square deviation, variation coefficient; determination of the amplitude of blood flow oscillations in different frequency range (by laser doppler flowmetry method). Results. Dimephosphon stimulates oscillatory and non-oscillatory skin microhaemodynamic indiсes indicating the increase of peripheral tissues perfusion and blood flow modulation in microvessels due to endothelium functional activity increase, peripheral resistance decrease, increase of blood flow to the nutritive microvessel channel and venous outflow improvement. Conclusion. Vasoactive properties of dimephosphon are manifested in its ability to affect vascular and extravascular regulatory processes of blood microcirculation of skin. Microvessel endothelium and its metabolic activity associated with NO release are the most sensitive to dimephosphon effect. The ability to increase endothelium NO production is the basic mechanism of dimephosphon vasodilatory action.

Локальные гипертонические эффекты сосудистой нагрузки сердца при выполнении упражнений гимнастики «Пилатес»

The effects of adaptation of cardiovascular system during muscular work and after completion are characterized by a certain agreed set of indicators of central hemodynamics, vascular workload of the heart and its contractility. The coordinated changing of hemodynamics and interactions indices of heart and vessels are determined by a functional subject´s state and also by capacity of the work performed by the relevant muscle groups. It is shown that when performing certain exercises of gymnastics Pilates, the values of vascular resistance (under normal systolic and diastolic blood pressure) can reach values of hypertensive level (over 2000 din-c/cm5 for peripheral vascular resistance - R and over 2000 din/cm5 for elastic vascular resistance - Ea). Such values of vascular resistance, as vascular load of the heart, are obtained during a transitional process with proper voltage group of postural muscles that provide the ability to perform certain exercises Pilates. In contrast to dynamic physical exercises, for example cycling, exercises Pilates are performed in quasi-static mode. In both cases, there is the growth of elastic vascular resistance, but in dynamic mode there is a fairly dramatic decrease in peripheral resistance, and in the quasi-static regime - an increasing EA simultaneously with the increase in peripheral resistance R.

THERAPEUTIC EFFECTS OF CARBONATED MINERAL WATERS IN CARDIOVASCULAR REHABILITATION

Carbonated water baths represent a method used for the prevention and treatment of cardiovascular diseases in some spa resorts in Romania. Carbonated mineral waters are the result of the filtration of depth waters through volcanic soils that contain carbon dioxide. The most important effect is the direct effect of carbon dioxide, which is absorbed through the skin, with an absorption coefficient of 30-35 ml/min/sqm body surface area. An excitation of vascular receptors and a dilation of dermal papillae, responsible for skin erythema, occur. The effects of the carbonated water bath on the cardiovascular system are the following: decrease of peripheral resistance by the direct action of carbon dioxide on arterioles and arteriovenous anastomoses; increase of both systolic and diastolic cardiac output, not by central mechanism as in the case of hot baths, but initially, by passive peripheral vasodilation, without increased venous return; subsequently, by accumulation in the cutaneous venous system, venous return towards the right heart will be increased, with a higher diastolic filling and a higher stroke volume. Carbonated water baths increase arteriolar blood flow in the skin, the vasodilator effect being directly proportional to the carbon dioxide concentration in the mineral bath. The effect of external carbonated water treatment is based on mechanical and thermal action, as well as on the chemical properties of carbon dioxide, its influence being either local or postabsorptive. Carbonated water baths are a therapeutic method that is also used in the treatment facilities of the Baile Tusnad spa resort, under the supervision of qualified medical experts, in a pleasant environment close to nature.

Evaluation of cardiovascular effects of edible fruits of <i>Syzygium cumini</i> Myrtaceae (L) skeels in rats

Purpose: To evaluate the hypotensive, vasorelaxant and antihypertensive effects elicited by the hydroalcohol extract from the fruits of Syzygium cumini (EHSCF) in non-anesthetized rats. Methods: The rats were anesthetized and polyethylene catheters were inserted into the lower abdominal aorta and into the inferior vena cava for blood pressure measurements and administration of drugs. After a recovery period of 24 h, EHSCF (0.5; 1; 5; 10; 20 and 30 mg/kg, i.v.) was administered in non-anesthetized rats. The mean arterial pressure and the heart rate were recorded. To investigate the effects of extract, doses EHSCF were administered after pretreatment with L-NAME, atropine, indomethacin, and hexamethonium. For measurement of isometric tension, a concentration-response curve was obtained after Phenylephrine and KCl (80 mM) pre-contractions. The bioactive extract was analyzed via mass spectrometry (MS) fingerprinting using direct electrospray ionization mass spectrometry (ESI-MS). Results: EHSCF (0.5; 1; 5; 10; 20 and 30 mg/kg) induced hypotension (-15 ± 1, -14 ± 1, -15 ± 1, -13 ± 1, -11 ± 1 and -13 ± 2 %) and bradycardia (-6 ± 1, -5 ± 1, -6 ± 1, -14 ± 1, -8 ± 1 and -10 ± 2 %) in normotensive rats. These responses were attenuated by pre-treatment with L-NAME, indomethacin, hexamethonium or atropine. In phenylephrine, pre-contracted mesenteric rings, EHSCF-induced relaxation (Emax = 54.6 ± 4.5 % and pD2 = 2.7 ± 0.1) that were affected by endothelium removal. EHSCF caused relaxant effect of KCl (80 mM) pre-contracted rings (Emax = 100 ± 0.2 % and pD2 = 2.2 ± 0.1). This effect was not changed in denuded rings. A single oral administration of the extract reduced significant mean arterial pressure in spontaneously hypertensive rats. ESI-MS/MS analyses of EHSCF demonstrated that the major constituents of the analyzed samples coincided with the mass of the malic, gallic, caffeic and ferulic acids. Conclusion: The results suggest that EHSCF induces hypotension probably due to a decrease in peripheral resistance, mediated by the endothelium. Bradycardia may be due to indirect cardiac muscarinic activation. The extract also causes an antihypertensive effect.

Azilsartan alone and in combination for the treatment of hypertension – clinical utility and patient considerations

Correspondence: Sylvia H Jackson Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, 2050 Art Museum Drive, Suite 200, Jacksonville, FL 32207, USA Tel +1 904 391 3904 Fax +1 904 391 3915 Email sylvia.jackson@famu.edu Abstract: Hypertension is a common disease that leads to significant cardiovascular morbidity and mortality. Adequate blood pressure control is essential in preventing end organ complications. One of the most popular antihypertensive strategies for the treatment of elevated blood pressure is to attenuate the actions of the renin-angiotensin-aldosterone system. The agents include the angiotensin converting enzyme inhibitors, angiotensin II receptor blockers (ARBs), direct renin inhibitors, and aldosterone antagonists. The ARBs inhibit the action of angiotensin II by binding to the angiotensin II type 1 receptor. The inhibition of angiotensin II results in a dose dependent decrease in peripheral resistance, reduction in vascular smooth muscle contraction, and reduced synthesis of aldosterone in the kidneys. Azilsartan medoxomil is a highly selective ARB. It was approved by the US Food and Drug Administration in February 2011 for the treatment of hypertension in adults. It is the eighth ARB to be added to the market. This article will discuss the pharmacologic and clinical characteristics of azilsartan medoxomil to help differentiate it from other ARBs that are used for the management of hypertension.

The effects of low‐dose epinephrine infusion on spleen size, central and hepatic circulation and circulating platelets

In several conditions associated with adrenergic stimulation, an increase in peripheral count of larger platelets has been observed, but the mechanism remained elusive. Larger platelets have greater prothrombotic potential and increase the risk of acute thrombotic events. The human spleen retains one-third of total body platelets, with mean volume (MPV) about 20% greater than that of circulating platelets. We aimed to answer whether low-dose epinephrine infusion results in spleen contraction and MPV increase. We undertook the continuous ultrasonic measurements of spleen volume, hepatic and central circulation with concurrent blood sampling in response to intravenous infusion of epinephrine (6 min of 0·06 µg kg(-1) per min, followed by 3 min of 0·12 µg kg(-1) per min) in nine healthy young subjects. The spleen volume started to decrease immediately after the onset of infusion, in the presence of substantial decreases in peripheral resistance and mean blood pressure and increases in heart rate and cardiac output. The majority of spleen emptying, approximately 25%, (95% CI 71·3-299·7) was observed 1 min after infusion onset, the hepatic vein flow peaked at the end of infusion for 28·4% (95% CI 1074·6-407·9), while increases in platelet count for approximately 31% (95% CI 187·8-314·8) and MPV for 4·4% (95% CI 7·3-10·9) lagged until 1 min after infusion cessation. We suggest that spleen is a dynamic reservoir of large platelets, which are mobilized even by low-dose epinephrine infusion in conditions of decreased blood pressure.

Increased Proximal Arterial Stiffness and Cardiac Response With Moderate Exercise in Patients With Heart Failure and Preserved Ejection Fraction

This study sought to demonstrate that arterial stiffness is probably underestimated in patients with heart failure with preserved ejection fraction (HFpEF) at rest and may be revealed with moderate exercise. HFpEF is associated with ventriculoarterial stiffening. We compared 23 patients with stable chronic HFpEF, left ventricular ejection fraction >45%, and impaired relaxation with 15 controls without cardiac disease. Patients were compared at rest and during a 30-W exercise. The following variables were measured or calculated by Doppler echocardiography and tonometry: left ventricular volumes and end-systolic elastance (Ees), peripheral resistance, arterial elastance (Ea), arterial compliance, aortic pulse wave velocity, and carotid Peterson modulus (Ep). Patients with HFpEF were comparable to controls in age, sex ratio, blood pressure, and heart rate. Ventriculoarterial coupling, assessed by Ees/Ea and Ees/Ep ratios, was moderately impaired at rest in patients compared with controls (both p < 0.01). HFpEF was associated during exercise with a major increase in Ep (+155 ± 193% vs. -5 ± 28%), pulse wave velocity (+20 ± 30% vs. -7 ± 24%), and Ea (+12 ± 15% vs. -5 ± 10%), and a lower decrease in peripheral resistance (-17 ± 12% vs. -26 ± 12%) (p < 0.05 for all). In addition, HFpEF patients showed a lower increase in stroke volume (+10 ± 16% vs. +21 ± 12%) despite a greater increase in Ees (+20 ± 18% vs. +3 ± 12%) (p < 0.05 for all). Also during exercise, adaptation of proximal ventriculoarterial coupling was impaired in HFpEF patients (Ees/Ep: -26 ± 47% vs. +20 ± 47% for controls) (p < 0.01), with no difference in Ees/Ea. In HFpEF patients, moderate exercise leads to a steep increase in proximal afterload that is underestimated at rest and is associated with unfavorable ventriculoarterial coupling and exercise intolerance.

Effects of successive air and nitrox dives on human vascular function

SCUBA diving is regularly associated with asymptomatic changes in cardiac, pulmonary and vascular function. The aim of this study was to evaluate the changes in vascular/endothelial function following SCUBA diving and to assess the potential difference between two breathing gases: air and nitrox 36 (36% oxygen and 64% nitrogen). Ten divers performed two 3-day diving series (no-decompression dive to 18 m with 47 min bottom time with air and nitrox, respectively), with 2 weeks pause in between. Arterial/endothelial function was assessed using SphygmoCor and flow-mediated dilation measurements, and concentration of nitrite before and after diving was determined in venous blood. Production of nitrogen bubbles post-dive was assessed by ultrasonic determination of venous gas bubble grade. Significantly higher bubbling was found after all air dives as compared to nitrox dives. Pulse wave velocity increased slightly (~6%), significantly after both air and nitrox diving, indicating an increase in arterial stiffness. However, augmentation index became significantly more negative after diving indicating smaller wave reflection. There was a trend for post-dive reduction of FMD after air dives; however, only nitrox diving significantly reduced FMD. No significant differences in blood nitrite before and after the dives were found. We found that nitrox diving affects systemic/vascular function more profoundly than air diving by reducing FMD response, most likely due to higher oxygen load. Both air and nitrox dives increased arterial stiffness, but decreased wave reflection suggesting a decrease in peripheral resistance due to exercise during diving. These effects of nitrox and air diving were not followed by changes in plasma nitrite.

Haemodynamic consequences of changing potassium concentrations in haemodialysis fluids

BackgroundA rapid decrease of serum potassium concentrations during haemodialysis produces a significant increase in blood pressure parameters at the end of the session, even if effects on intra-dialysis pressure are not seen. Paradoxically, in animal models potassium is a vasodilator and decreases myocardial contractility. The purpose of this trial is to study the precise haemodynamic consequences induced by acute changes in potassium concentration during haemodialysis.MethodsIn 24 patients, 288 dialysis sessions, using a randomised single blind crossover design, we compared six dialysate sequences with different potassium profiles. The dialysis sessions were divided into 3 tertiles, casually modulating potassium concentration in the dialysate between the value normally used K and the two cut-off points K+1 and K-1 mmol/l. Haemodynamics were evaluated in a non-invasive manner using a finger beat-to-beat monitor.ResultsComparing K-1 and K+1, differences were found within the tertiles regarding systolic (+5.3, +6.6, +2.3 mmHg, p < 0.05, < 0.05, ns) and mean blood pressure (+4.3, +6.4, -0.5 mmHg, p < 0.01, < 0.01, ns), as well as peripheral resistance (+212, +253, -4 dyne.sec.cm-5, p < 0.05, < 0.05, ns). The stroke volume showed a non-statistically-significant inverse trend (-3.1, -5.2, -0.2 ml). 18 hypotension episodes were recorded during the course of the study. 72% with K-1, 11% with K and 17% with K+1 (p < 0.01 for comparison K-1 vs. K and K-1 vs. K+1).ConclusionsA rapid decrease in the concentration of serum potassium during the initial stage of the dialysis-obtained by reducing the concentration of potassium in the dialysate-translated into a decrease of systolic and mean blood pressure mediated by a decrease in peripheral resistance. The risk of intra-dialysis hypotension inversely correlates to the potassium concentration in the dialysate.Trial Registration NumberNCT01224314

The role of peripheral vascular resistance in determining the infrainguinal arterial reconstruction patency

To find if there is any correlation between the peripheral vascular resistance, its change following an intragraft prostaglandin infusion and the infrainguinal reconstruction patency. Ninety-seven patients with infrainguinal reconstructions were included in the study: in 48 patients they were compromised (32 with graft thrombosis and 16 with stenosis of the distal anastomoses); 49 patients had their bypasses patent for no less than 12 months. Intraoperative flowmetry was performed on the target artery under the distal anastomosis, after declamping, and after a five-minute intragraft prostaglandin infusion. We measured the peripheral vascular resistance (PVR) by two methods - as a ratio of the invasively measured average pressure to the average blood flow volume (mmHg/ml/min. = peripheral resistance unit [PRU]) and by using the readings by the flowmeter (ohms). The decrease of peripheral resistance was calculated in the functioning and the compromised reconstructions after administration of prostaglandin. We found that if PVR decreases 4.5 times (in ohms) the prognosis is good; we can make the same positive prognosis when the ratio of the mean invasively measured pressure to the mean blood flow volume (Pmean/Qmean) decreases more than four times. Values greater than 1.07 ohms, after peripheral vasodilatation, are indicative of high peripheral vascular resistance, at a level of specificity of 86%, and values greater than 0.57 PRU - at a level of specificity of 87%. Although PVR measurements cannot predict with absolute certainty that bypasses under the inguinal ligament shall stay patent for a long time, it is a valuable indicator showing the immediate outcome of reconstruction work carried out with the patient on the operating table. Finding Any technical errors and dealing with them saves time and money, as well as prevents the stress on the part of patients caused by the required additional revisions and multiple operations.

VS01 HYPERTENSIVE EXTRACORPOREAL LIMB PERFUSION – HELP

Objective: To report the early human results of H.E.L.P. technology in the prevention of major limb amputation. In the short‐term, the aim was to pressure dilate collateral channels and in the long‐term to stimulate remodelling and new collateral pathways by increasing endothelial shear stress.Methods: A pilot study consisted of the ischaemic limbs of 15 patients with critical limb ischaemia. These patients had no other option but major amputation as determined by at least two vascular surgeons. The limbs were connected to a commercially available cardiac pump via an access system. The limbs were hyperperfused pancycle at 2–3 times the mean arterial pressure (MAP). This was performed intermittently in sessions of 24–36 hours. The major endpoint was avoidance of major amputation.Results: Given adequate arterial access, 29 of 30 connections developed flows 4–8 times the MAP. There was a progressive decrease in peripheral resistance. All patients developed a pain‐free, warm foot or hand whilst on the pump in the short‐term. In the longer term, a mean of 10.4 months (range 1–29 months) 50% had avoided major amputation. Pain scores changed from 0.9 ± 0.1 to 1.1 ± 1.3 under the visual analogue scale (V.A.S). The ankle brachial index (A.B.I) changed from 0.06 ± 0.09 to 0.57 ± 0.33, p &lt; 0.05 (t test).Conclusions: The collateral circulation of ischaemic limbs can be augmented and regulated via connection to an extracorporeal cardiac pump. The technique is similar to haemodialysis. Major amputation can be avoided in selective cases. Improvements in the technology are continuing.

Response to Letter Regarding Article, “Continuous Aortic Flow Augmentation: Not Enough MOMENTUM”

I agree with the objection raised by Dr Greenberg about my comment1 that implied that the continuous aortic flow augmentation system had a primary or direct effect on increasing cardiac output. Clearly, any increase in cardiac output would be secondary to a decrease in peripheral resistance associated with the distal aortic perfusion. The study design used in the Multicenter Trial of the Orqis Medical Cancion System for the Enhanced Treatment of Heart Failure Unresponsive to Medical Therapy (MOMENTUM) did in fact include a paired analysis, as noted by Dr Greenberg. The population of patients who develop worsening heart failure and become progressively unresponsive …

Immediate Effect of Slow PaceBhastrika Pranayamaon Blood Pressure and Heart Rate

The objective of this study was to evaluate the immediate effect of slow pace bhastrika pranayama (respiratory rate 6/min) for 5 minutes on heart rate and blood pressure and the effect of the same breathing exercise for the same duration of time (5 minutes) following oral intake of hyoscine-N-butylbromide (Buscopan), a parasympathetic blocker drug. Heart rate and blood pressure of volunteers (n = 39, age = 25-40 years) was recorded following standard procedure. First, subjects had to sit comfortably in an easy and steady posture (sukhasana) on a fairly soft seat placed on the floor keeping head, neck, and trunk erect, eyes closed, and the other muscles reasonably loose. The subject is directed to inhale through both nostrils slowly up to the maximum for about 4 seconds and then exhale slowly up to the maximum through both nostrils for about 6 seconds. The breathing must not be abdominal. These steps complete one cycle of slow pace bhastrika pranayama (respiratory rate 6/min). During the practice the subject is asked not to think much about the inhalation and exhalation time, but rather was requested to imagine the open blue sky. The pranayama was conducted in a cool, well-ventilated room (18-20 degrees C). After 5 minutes of this breathing practice, the blood pressure and heart rate again were recorded in the aforesaid manner using the same instrument. The other group (n = 10) took part in another study where their blood pressure and heart rate were recorded following half an hour of oral intake of hyoscine-N-butylbromide 20 mg. Then they practiced the breathing exercise as stated above, and the abovementioned parameters were recorded again to study the effect of parasympathetic blockade on the same pranayama. It was noted that after slow bhastrika pranayamic breathing (respiratory rate 6/min) for 5 minutes, both the systolic and diastolic blood pressure decreased significantly with a slight fall in heart rate. No significant alteration in both blood pressure and heart rate was observed in volunteers who performed the same breathing exercise for the same duration following oral intake of hyoscine-N-butylbromide. Pranayama increases frequency and duration of inhibitory neural impulses by activating pulmonary stretch receptors during above tidal volume inhalation as in Hering Bruer reflex, which bring about withdrawal of sympathetic tone in the skeletal muscle blood vessels, leading to widespread vasodilatation, thus causing decrease in peripheral resistance and thus decreasing the diastolic blood pressure. After hyoscine-N-butylbromide, the parasympathetic blocker, it was observed that blood pressure was not decreased significantly as a result of pranayama, as it was observed when no drug was administered. Vagal cardiac and pulmonary mechanisms are linked, and improvement in one vagal limb might spill over into the other. Baroreceptor sensitivity can be enhanced significantly by slow breathing (supported by a small reduction in the heart rate observed during slow breathing and by reduction in both systolic and diastolic pressure). Slow pace bhastrika pranayama (respiratory rate 6/min) exercise thus shows a strong tendency to improving the autonomic nervous system through enhanced activation of the parasympathetic system.

The acute post-exercise response of blood pressure varies with time of day

The reactivity of ambulatory blood pressure following a given change in everyday physical activities is highest in the morning. Whether the acute response of blood pressure following a controlled bout of steady-state exercise is influenced by time of day is examined in this study. After 45 min of supine rest, 12 male normotensives completed 30 min of cycling at 70% VO(2peak) which began at either 0800 or 1600 hours. Arterial blood pressure, cardiac output, total peripheral resistance, cutaneous blood flow and temperature were determined before, and up to 90 min after, exercise. Mean +/- SE arterial pressure, averaged over the acute (20-min) period, reduced by 7 +/- 2 mmHg following exercise at 1600 hours but increased by 3 +/- 3 mmHg following exercise at 0800 hours (P = 0.03). Total peripheral resistance fell by 4.2 +/- 0.8 mmHg l(-1) min(-1) after exercise at 1600 hour, but increased slightly by 0.1 +/- 0.5 mmHg l(-1) min(-1) after morning exercise (P = 0.02). We conclude that the acutely hypotensive effects following 30 min of steady state exercise are less marked in the morning, probably because the exercise-mediated decrease in peripheral resistance is not as apparent at this time of day.

Different Pharmacological Properties of Two Enantiomers in a Unique β‐Blocker, Nebivolol

Nebivolol is a racemic combination of d-nebivolol (+SRRR nebivolol) and l-nebivolol (-RSSS nebivolol) that differs chemically from other beta-blockers, with an absolutely symmetrical configuration developing from a central nitrogen atom. D-nebivolol and l-nebivolol divaricate pharmacologically and therapeutically, with a noticeably different profile from that of conventional beta-blockers; for instance, the selective blocking of beta(1)-adrenoceptors is determined almost exclusively by d-nebivolol. Both enantiomers act synergistically with respect to blood pressure reduction: the effect of nebivolol on heart rate is exclusively exerted by d-nebivolol, with these hypotensive effects enhanced by the addition of the l-enantiomer, which in itself does not influence systolic and diastolic blood pressure. Furthermore, this pronounced and lasting blood pressure reduction is roughly equal to the effect of conventional beta-blockers in high doses. In certain vascular districts, nebivolol stimulates endothelial nitric oxide (NO) synthesis, thereby increasing the availability of NO in the endothelium, smooth muscle, and platelets and, consequently, producing a sustained vasodilation, with decreases in peripheral resistance and blood pressure. These effects are not shared by other beta-adrenoceptor blockers used as references and mainly rely on the l-enantiomer. L-nebivolol also increases NO availability under conditions of oxidative stress by the inhibition of endothelial NO synthase (eNOS) uncoupling, thereby reducing NO inactivation. Furthermore, neither nebivolol nor its enantiomers show any intrinsic sympathomimetic activity and undesirable beta-blocker effects, such as a decrease in cardiac output, which do not occur or are less pronounced with the combination of d-nebivolol and l-nebivolol. In conclusion, the independent pharmacologic and clinical effects of d-nebivolol and l-nebivolol act synergistically to produce a cardiovascular profile that differs noticeably from that of conventional beta-blockers.

Doppler ultrasound in cases of Rhesus incompatibility. Effect of intravascular punctures with or without transfusion on feto-placental Doppler blood flow velocity curves

To investigate the influence of cordocentesis with or without blood transfusion on umbilical and fetal blood flow characteristics. Of 42 pregnant women suffering from Rh. incompatibility 15 had a puncture of the umbilical cord for diagnostic reasons only. In 27 cases a total of 86 punctures was done for blood transfusion. Fetal heart rate, umbilical artery A/B Ratio and Pulsatility Index (PI) in the fetal aorta were measured before and after cordocentesis in all cases having or having not a transfusion. Diagnostic and therapeutic cordocentesis resulted in a slight decrease of peripheral resistance. Significant differences were only observed in cases with a haematocrit < 20% compared to cases with values > 40% or if the final haematocrit after transfusion resulted in a value of < 30%. The decrease peripheral resistance in cases of therapeutic cordocentesis can be attributed to the increase in blood volume and sufficient oxygenation of blood improving fetal perfusion. Doppler sonography is not helpful in the clinical management of red blood cell immunisation.

Cardiovascular Reactivity During Positive and Negative Marital Interactions

Marriage reduces risk of cardiovascular disease (CVD) but marital stress increases risk, perhaps through cardiovascular reactivity (CVR). However, previous studies have lacked controls necessary to conclude definitively that negative marital interactions evoke heightened CVR. To test the specific effects of marital stress on CVR, 114 couples engaged in positive, neutral, or negative interactions in which speaking and task involvement were controlled. Compared to positive and neutral conditions, negative discussions evoked larger increases in systolic blood pressure, heart rate, and cardiac output, and larger decreases in peripheral resistance and pre-ejection period--similarly for men and women. Hence, CVR could contribute to the effects of marital difficulties on CVD. Previous evidence of sex differences in this effect might reflect factors other than simple reactivity to negative interactions.

Function and form—a chicken and egg situation

Function and form—a chicken and egg situation

VASODILATOR EFFECTS OF LEPTIN ON CANINE ISOLATED MESENTERIC ARTERIES AND VEINS

1. Although leptin increases sympathetic nerve activity and blood pressure, its direct action on large arterial rings is to cause relaxation. However, it is the small resistance arteries and veins that are important in blood pressure control. The effects of leptin on these small vessels has not been reported previously in the canine and the effect of leptin on the capacitance vessels is not known. 2. In the present study, third- or fourth-order canine mesenteric arteries and veins were isolated and placed in a perfusion myograph and preconstricted with noradrenaline. The responses to graded concentrations of leptin were determined and the role of nitric oxide was assessed by administration of N(G)-nitro-l-arginine methyl ester (l-NAME), a blocker of nitric oxide synthase. 3. Leptin induced dose-related dilatations in both arterial and venous segments. The mean (+/-SEM) maximum increases in the diameter of the arteries and veins were 25.0 +/- 4.8 and 29.9 +/- 2.0% of the initial preconstriction, respectively. Relaxations of both arteries and veins were abolished by l-NAME or by endothelium denudation, although dilatations were still obtained to sodium nitroprusside, a nitric oxide donor. 4. These results indicate that leptin dilates canine small mesenteric arteries and veins by a mechanism involving endothelial release of nitric oxide. This observation may result in a decrease of peripheral resistance and venous return and, hence, counteract the leptin-induced neurally mediated vasoconstriction that has been reported previously.