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PubMed2000

Cardiovascular response to acute hypovolemia in relation to age. Implications for orthostasis and hemorrhage.

Venous compliance in the legs of aging man has been found to be reduced with decreased blood pooling (capacitance response) in dependent regions, and this might lead to misinterpretations of age-related changes in baroreceptor function during orthostasis. The hemodynamic response to hypovolemic circulatory stress was studied with the aid of lower-body negative pressure (LBNP) of 60 cmH(2)O in 33 healthy men [18 young (mean age 22 yr) and 15 old (mean age 65 yr)]. Volumetric technique was used in the study of capacitance responses in the calf and arm as well as transcapillary fluid absorption in the arm. LBNP led to smaller increase in heart rate (P < 0.001) and peripheral resistance (P < 0.01) and reduced transcapillary fluid absorption in the arm (P < 0.05) in old subjects. However, blood pooling in the calf was reduced in old subjects (1.66 +/- 0.10 vs. 2.17 +/- 0.13 ml/100 ml tissue; P < 0. 01). Accordingly, during similar blood pooling in the calf (LBNP 80 cmH(2)O in old subjects), no changes in cardiovascular reflex responses with age were found. The capacitance response in the arm (mobilization of peripheral blood to the central circulation) was still reduced, however (0.67 +/- 0.10 vs. 1.37 +/- 0.11 ml/100 ml tissue; P < 0.01). Thus the reduced cardiovascular reflex response found in the elderly during orthostatic stress seems to be caused by a reduced capacitance response in the legs with age and a concomitant smaller central hypovolemic stimulus rather than a reduced efficiency of the reflex response. With similar hypovolemic circulatory stress, no changes in cardiovascular reflex responses are seen with age. The capacitance response in the arm (mobilization of peripheral blood toward the central circulation) is reduced, however, by approximately 50% in the elderly. This might seriously impede the possibility of survival of an acute blood loss.

Acute Disease↗
PubMed2000

Regulation of the venous capacitance during microgravity.

The purpose of this paper is to report our recent investigations on the relationship between sympathetic tone and leg venous compliance, as well as on the baroreflex control of leg venous compliance after simulated microgravity exposure in healthy humans.

Baroreflex↗
PubMed1999

Focal agonist stimulation results in spatially restricted Ca2+ release and capacitative Ca2+ entry in bovine vascular endothelial cells.

1. Intracellular Ca2+ ([Ca2+]i) signals were studied with spatial resolution in bovine vascular endothelial cells using the fluorescent Ca2+ indicator fluo-3 and confocal laser scanning microscopy. Single cells were stimulated with the purinergic receptor agonist ATP resulting in an increase of [Ca2+]i due to intracellular Ca2+ release from inositol 1,4,5-trisphosphate (IP3)-sensitive stores. ATP-induced Ca2+ release was quantal, i.e. submaximal concentrations mobilized only a fraction of the intracellularly stored Ca2+. 2. Focal receptor stimulation in Ca2+-free solution by pressure application of agonist-containing solution through a fine glass micropipette resulted in a spatially restricted increase in [Ca2+]i. Ca2+ release was initiated at the site of stimulation and frequently propagated some tens of micrometres into non-stimulated regions. 3. Local Ca2+ release caused activation of capacitative Ca2+ entry (CCE). CCE was initially colocalized with Ca2+ release. Following repetitive focal stimulation, however, CCE became detectable at remote sites where no Ca2+ release had been observed. In addition, the rate of Ca2+ store depletion with repetitive local activation of release in Ca2+-free solution was markedly slower than that elicited by ATP stimulation of the entire cell. 4. From these experiments it is concluded that both intracellular IP3-dependent Ca2+ release and activation of CCE are controlled locally at the subcellular level. Moreover, redistribution of intracellular Ca2+ stored within the endoplasmic reticulum efficiently counteracts local store depletion and accounts for the spatial spread of CCE activation.

Action Potentials↗
PubMed2005

Cardiac preload and venous return in swimming sea bass (Dicentrarchus labrax L.).

Cardiac preload (central venous pressure, P(CV), mean circulatory filling pressure (MCFP), dorsal aortic blood pressure (P(DA)) and relative cardiac output (Q) were measured in sea bass (Dicentrarchus labrax) at rest and while swimming at 1 and 2 BL s(-1). MCFP, an index of venous capacitance and the upstream venous pressure driving the return of venous blood to the heart, was measured as the plateau in Pcv during ventral aortic occlusion. Compared with resting values, swimming at 1 and 2 BL s(-1) increased Q (by 15+/-1.5 and 38+/-6.5%, respectively), P(CV) (from 0.11+/-0.01 kPa to 0.12+/-0.01 and 0.16+/-0.02 kPa, respectively), MCFP (from 0.27+/-0.02 kPa to 0.31+/-0.02 and 0.40+/-0.04 kPa, respectively) and the calculated pressure gradient for venous return (DeltaP(V), from 0.16+/-0.01 kPa to 0.18+/-0.02 and 0.24+/-0.02 kPa, respectively), but not P(DA). In spite of an increased preload, the increase in Q was exclusively mediated by an increased heart rate (f(H), from 80+/-4 beats min(-1) to 88+/-4 and 103+/-3 beats min(-1), respectively), and stroke volume (Vs) remained unchanged. Prazosin treatment (1 mg kg(-1) Mb) abolished pressure and flow changes during swimming at 1 BL s(-1), but not 2 BL s(-1), indicating that other control systems besides an alpha-adrenoceptor control are involved. This study is the first to address the control of venous capacitance in swimming fish. It questions the generality that increased Q during swimming is regulated primarily through Vs and shows that an increased cardiac filling pressure does not necessarily lead to an increased Vs in fish, but may instead compensate for a reduced cardiac filling time.

Animals↗
PubMed2002

Computer systems analysis of the cardiovascular mechanisms of reentry orthostasis in astronauts.

Reentry orthostasis secondary to a prolonged exposure to microgravity is a common problem among astronauts. However, the physiologic mechanisms are poorly understood due to the many control systems involved. In this study an advanced computer model of cardiovascular functioning was employed in a systems analysis approach to clarify the relative importance of some of the adaptive physiologic processes engaged when humans return from space. After simulation of the conditions of zero gravity for one month, the model predicted that the change in capacitance of the lower extremity veins resulting from a loss of external fluid forces in the dehydrated extracellular compartment was the dominant mechanism associated with reentry orthostasis. This condition appears accentuated in women due to their inherent lower center of gravity and proportionately larger mass in the lower extremities.

Adaptation, Physiological↗
PubMed2002

Altered venous function and deep venous thrombosis following proximal femoral fracture.

The effect of surgery for femoral neck fracture on lower limb venous blood flow and its relationship to deep vein thrombosis was investigated in 179 patients. Blood flow was measured using strain gauge plethysmography before surgery, in the 1st week after surgery, and at 6 week review. There was a significant reduction in both venous outflow and venous capacitance, affecting both fractured and non-fractured legs but significantly greater in the fractured leg. Venous function remained significantly impaired in both lower limbs 6 weeks after surgery. There was a significant correlation between the reduction in venous function and the development of deep vein thrombosis.

Aged↗
PubMed2006

A low plasma volume in formerly preeclamptic women predisposes to the recurrence of hypertensive complications in the next pregnancy.

BACKGROUND: Formerly preeclamptic women with a subnormal plasma volume (PV) have an increased risk to develop a hypertensive disorder in a subsequent pregnancy as compared to women with normal PV. In the current study we tested the hypothesis that formerly preeclamptic women who develop recurrent disease in their next pregnancy differ from their counterparts with an uneventful next pregnancy by a lower pre-pregnant PV, a lower venous capacitance, smaller rises in these indices in early pregnancy, a lower renal adaptive response, and a lower response to mild exercise. PATIENTS AND METHODS: We enrolled 33 formerly preeclamptic women in this study. Only 14 conceived within the study period, with seven of them developing a recurrent hypertensive disorder in their next pregnancy (RECUR), while seven had an uneventful next pregnancy (NORM). Before pregnancy and at 12 weeks of gestational age, we compared the following variables between these subgroups: PV, venous capacitance, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), and the responses in stroke volume (SV) and heart rate (HR) to mild exercise. To estimate venous capacitance, we infused 500 mL of a modified gelatine solution in 30 minutes while recording the change in cardiac output (pulse contour analysis). The ratio of percent change in blood volume to percent change in cardiac output in response to a standardized small volume load provides an estimate for venous capacitance. RESULTS: RECUR differed from NORM by a 20% lower pre-pregnant PV (P <.02) and venous capacitance (0.29 [0.11-0.55] vs 0.86 [0.64-2.03] P = .002). NORM and RECUR were comparable with respect to pregnancy-induced rise in PV, renal hemodynamics and function, and response to mild exercise at 12 weeks. Newborn weight correlated positively with pre-pregnancy PV (R(2) = 0.53 and P = .04). CONCLUSION: Formerly preeclamptic women with a recurrent hypertensive disorder in their next pregnancy differed from their counterparts with an uneventful next pregnancy by a lower pre-pregnant PV and a lower venous capacitance, the latter two indices correlating also inversely with the incidence of fetal growth restriction. The preserved acute response to volume-related stimuli in women with a low pre-pregnant PV supports the view that the predisposition of low pre-pregnant PV to adverse pregnancy outcome may result from a concomitant, PV-dependent change setpoint and/or gain in the stimulus/response interrelation of the volume regulatory system.

Adult↗
PubMed1997

Efficacy of compression of different capacitance beds in the amelioration of orthostatic hypotension.

Orthostatic hypotension (OH) is the most disabling and serious manifestation of adrenergic failure, occurring in the autonomic neuropathies, pure autonomic failure (PAF) and multiple system atrophy (MSA). No specific treatment is currently available for most etiologies of OH. A reduction in venous capacity, secondary to some physical counter maneuvers (e.g., squatting or leg crossing), or the use of compressive garments, can ameliorate OH. However, there is little information on the differential efficacy, or the mechanisms of improvement, engendered by compression of specific capacitance beds. We therefore evaluated the efficacy of compression of specific compartments (calves, thighs, low abdomen, calves and thighs, and all compartments combined), using a modified antigravity suit, on the end-points of orthostatic blood pressure, and symptoms of orthostatic intolerance. Fourteen patients (PAF, n = 9; MSA, n = 3; diabetic autonomic neuropathy, n = 2; five males and nine females) with clinical OH were studied. The mean age was 62 years (range 31-78). The mean +/- SEM orthostatic systolic blood pressure when all compartments were compressed was 115.9 +/- 7.4 mmHg, significantly improved (p < 0.001) over the head-up tilt value without compression of 89.6 +/- 7.0 mmHg. The abdomen was the only single compartment whose compression significantly reduced OH (p < 0.005). There was a significant increase of peripheral resistance index (PRI) with compression of abdomen (p < 0.001) or all compartments (p < 0.001); end-diastolic index and cardiac index did not change. We conclude that denervation increases vascular capacity, and that venous compression improves OH by reducing this capacity and increasing PRI. Compression of all compartments is the most efficacious, followed by abdominal compression, whereas leg compression alone was less effective, presumably reflecting the large capacity of the abdomen relative to the legs.

Adult↗
PubMed2000

Acute effects of smoking on human cerebral blood flow: a transcranial Doppler ultrasonography study.

Middle cerebral artery (MCA) flow velocity was continuously monitored during smoking in an observational study (n = 14) using transcranial Doppler (TCD) ultrasonography. Cerebral autoregulatory vasodilator capacitance under inspired CO2 challenge was also measured before smoking and at peak smoking effect. Several puffs on a single lighted cigarette over a period of five minutes acutely increased MCA mean flow velocity in every subject (group mean increase: 19%, individual increases ranged 2-64%) with a response onset and offset detectable within several seconds of beginning and ending smoking. The mechanism for the increase in MCA flow velocities appeared to be independent of the CO2 autoregulatory mechanism. Gender subgroup analysis showed smoking acutely suppressed the CO2 vasodilator capacitance by 56% in men but only by 5% in women (p = 0.05). The magnitude of the acute smoking-induced increases in MCA flow velocities appeared to be independent of the estimated cigarette yields for nicotine, carbon monoxide, and "tar." Smoking in healthy subjects acutely increased MCA mean flow velocity, which may reflect a global increase in cerebral blood flow via complex influences on the cerebral autoregulation.

Adult↗
PubMed2000

[Changes in the venous vessels capacitance in the cat forepaw in response to neurohumoral stimuli].

The trend in changes of the cat forepaw vessels' capacity was found to practically not differ from the trend in shifts in the vena cava anterior basin's capacity: in both areas the capacity decreases in response to pressor neurogenic stimuli and decreases or increases under the effects of pressor and depressor humoral stimuli. The data obtained suggest that the trend in shifts of the vena cava anterior basin's capacity under the effects of pressor humoral stimuli mainly depends on the skin-muscular area's vessels, whereas the trend in shifts of the vena cava anterior basin's capacity under the effects of depressor humoral stimuli depends, apparently, on the shifts in the brain vessels' capacity function.

Acetylcholine↗
PubMed1996

Orthostatic hypotension and the role of changes in venous capacitance.

We suggest a mechanism by which blood volume changes might explain the hypotension that, after space flight, often accompanies the return to normal gravity. Upon entering microgravity, peripheral veins may collapse and, because of volume redistribution, raise the pressure in the central venous compartment. After some time in space, homeostatic mechanisms may cause volume excretion and reduce the pressure in the central venous compartment to normal values. Upon return to normal gravity, peripheral veins may re-expand and distribute a reduced blood volume into an enlarged space, thus lowering pressure in the central venous compartment. This would reduce cardiac preload, output, and arterial pressure. To prevent this sequence of events, leg cuffs might be inflated before the end of the space flight to allow homeostatic mechanisms to increase blood volume to normal levels.

Blood Circulation↗
PubMed1997

Multiple exocytotic pathways in pancreatic beta cells.

Ca2+-dependent exocytotic pathways in mouse pancreatic beta cells were investigated using both capacitance measurement and amperometric detection of vesicular contents. Serotonin was preloaded into large dense-core vesicles for the amperometry. Exocytosis was induced by rapid elevation of cytosolic Ca2+ concentrations using caged-Ca2+ compounds. Capacitance measurement revealed two major components of exocytosis, and only the slow component was accompanied by amperometric events reflecting quantal serotonin secretion. Moreover, the fast and slow exocytoses induced the two forms of endocytosis that were reported to follow the exocytoses of small-clear and large dense-core vesicles, respectively. Interestingly, we recorded two types of responses of quantal events: in the type-1 response, most quantal events occurred with a delay of 0.2 s and were rapidly exhausted with a time constant of 1.7 s, while, in the type-2 response, quantal events occurred with a delay of 2.5 s and were sustained. This suggests the existence of two pathways or modes of the exocytosis involving large dense-core vesicles. Thus, we have revealed three exocytotic pathways with divergent fusion kinetics in beta cells, which provide a new basis for the understanding of the physiology and pathology of beta cells.

Animals↗
PubMed1998

Effects of PEEP on systemic venous capacitance.

The aim of the present study was to determine effects of positive end expiratory pressure (PEEP) application on peripheral venous capacitance and relate them to concomitant central hemodynamic disturbances. The venous volume-pressure (V/P) relationships were studied in 6 intact anesthetized pigs to describe the effects of PEEP on systemic venous compliance (computed as the slope of the V/P relationship) and unstressed volume (referred to as the extrapolated volume intercept). Cardiac volumes as well as partitioning of circulating blood volume between central (ITBV) and peripheral (PBV) compartments were assessed by thermo-dye dilution techniques. During a 15 cm H2O PEEP application, venous compliance was reduced by 48%, while unstressed volume was increased by 25% and peripheral blood pooling increased from 63 to 74%. As a result, left heart and right ventricular end diastolic volumes were decreased by 8% and by 44%, respectively. It is concluded that increased venous unstressed volume and reduced compliance depicted the distension of the venous tree secondary to PEEP which acted as an impediment to venous return. As a consequence, cardiac output was reduced because of decreased preload.

Animals↗
PubMed2000

Abnormal venous function in patients with homozygous sickle cell (SS) disease and chronic leg ulcers.

Chronic leg ulceration is a major cause of morbidity in homozygous sickle cell (SS) disease in Jamaica. These ulcers have features in common with venous ulcers in patients with a normal haemoglobin genotype (AA). Thus we sought to determine whether there is abnormal venous function in the legs of patients with SS disease who have ulcers. Experiments were performed on 15 SS patients with ulcers, and on 15 SS patients and 15 AA subjects with no history of leg ulcers. Changes in venous blood volume of the bottom one-third of the leg induced by venous occlusion and release were studied by air plethysmography, providing indices of segmental venous capacitance (SVC), maximal venous outflow (MVO) and venous emptying time (VET). The changes in volume (ambulatory volume change; AVC) induced by a period of leg exercise were also measured at the ankle (AVCa) and calf (AVCc); venous refilling times at these sites (RTa and RTc respectively) were also measured. Finally, cutaneous red blood cell flux recovery time (FRT) after ankle exercise was assessed by laser Doppler flowmetry. Measurements were also made of haematological variables. SVC, MVO and VET did not differ between the groups, indicating no deep venous obstruction in the SS patients with ulcers. AVCc, AVCa and RTc did not differ among the three subject groups. However, compared with AA subjects, SS patients with ulcers had reduced RTa and FRT. Moreover, RTa and FRT were further shortened in SS patients with ulcers relative to SS patients without ulcers. Since the levels of anaemia were similar in SS patients with and without ulcers, these differences cannot be attributed to differences in arterial flow secondary to anaemia. These results suggest abnormal venous function in SS patients with ulcers, relative to both AA subjects and SS patients without ulcers. We propose that there is incompetence of venous valves draining the ankle region of SS patients with ulcers: the consequent raised venous pressure contributes to the slow healing and, possibly, to the onset of leg ulceration in SS disease.

Adult↗
PubMed1997

Regional gradation of L-type calcium currents in the feline heart with a healed myocardial infarct.

INTRODUCTION: Abnormal action potentials in myocytes adjacent to > 2-month-old feline LV myocardial infarcts (MI) may reflect alterations in Ca2+ currents (Ica). METHODS AND RESULTS: We compared ICa, at 36 degrees C, in subendocardial myocytes isolated from areas adjacent to MI and to ICa in cells from remote areas (> 4 mm away; REM) and control cells from similar regions in normal hearts. Control (CON) myocytes had membrane capacitance of 234 +/- 10 pF (n = 81 cells) compared to 305 +/- 14 pF in REM (71 cells; P < 0.05 from CON) and 237 +/- 11 pF (n = 55 cells) in MI (not different from CON). From Vh = -40 mV; peak ICa elicited by test potentials (-35 to +70 mV) were significantly larger in CON (-1746 +/- 123 pA) and REM (-1795 +/- 142 pA) compared to MI (-1352 +/- 129 pA) (P < 0.05). Peak ICa density was significantly reduced in REM (-6.0 +/- 0.4 pA/pF) or MI (-5.7 +/- 0.4 pA/pF, P < 0.05) compared to CON (-7.5 +/- 0.4 pA/pF). Double exponential ICa decay was similar among groups. Half-inactivation potential (V0.5) was significantly shifted (hyperpolarizing direction) for MI (-29.1 +/- 2.6 mV) and REM (-24.6 +/- 1.2 mV) myocytes compared to -20.3 +/- 1.0 mV in CON. MI slope factor (k; 9.0 +/- 0.5) was significantly different from CON (6.8 +/- 0.3) and REM (7.3 +/- 0.4). No differences in time course of recovery from inactivation were noted. Five millimolar Ba2+o produced significant increases in ICa in CON and REM but an attenuated response in MI. Bay K8644 (1 microM) produced similar ICa increase in all groups. ICa increase due to isoproterenol (1 microM) in MI and REM was half that in CON, but there were no differences in increased ICa responses among groups following phenylephrine (10 microM). CONCLUSION: Reduced ICa density in REM reflects cell hypertrophy, whereas altered ICa of MI may reflect altered channel structure and/or function.

Action Potentials↗
PubMed2005

Formerly preeclamptic women with a subnormal plasma volume are unable to maintain a rise in stroke volume during moderate exercise.

INTRODUCTION: In formerly preeclamptic women with a low plasma volume, the recurrence rate of preeclampsia is higher than in women with a normal prepregnant plasma volume. In a recent study, we demonstrated that the low plasma volume subgroup also had a subnormal venous capacitance. In the present study, we determined the impact of subnormal plasma volume on the hemodynamic response to moderate exercise. PATIENTS AND METHODS: We performed this study in the follicular phase of the menstrual cycle, in 31 formerly preeclamptic women with a subnormal plasma volume (low-PV) and eight parous controls. The exercise consisted of 60 minutes of cycling in the supine position at 35% of the individualized maximum capacity. Before, during, and after cycling, we measured the percentage change in heart rate, stroke volume, and cardiac output. Before and after exercise, we measured the effective renal plasma flow (ERPF, para-amino-hippurate [PAH] clearance), glomerular filtration rate (GFR, inulin clearance), circulating levels of alpha-atrial natriuretic peptide (alpha-ANP), and active plasma renin concentration (APRC). RESULTS: The response to exercise of formerly preeclamptic women with a subnormal plasma volume differed from that in controls by a lack of rise in stroke volume, a smaller rise in cardiac output and alpha-ANP, and a greater fall in GFR. The responses in heart rate, ERPF, and APRC did not differ between the two groups. CONCLUSION: The response to moderate exercise of formerly preeclamptic women with a subnormal plasma volume differs from that in healthy parous controls with a normal plasma volume and suggests a lower capacity to raise venous return in conditions of a higher demand for systemic flow. The lower capacity to raise venous return in these conditions is associated with more cardiovascular drift. The physiologic consequence is a lower aerobic endurance performance during moderate exercise.

Adult↗
PubMed1998

Vascular volume determination of articular tissues in normal and anterior cruciate ligament-deficient rabbit knees.

The vasculature of diarthroidal joints has been well documented; however, the volume of vessels supplying different articular tissues is unknown. Angiogenesis, the formation of new vessels from preexisting ones, is difficult to quantify in joints due to the unavailability of a suitable technique. Although angiogenesis is known to occur in rheumatoid arthritis, the development of new vessels following joint injury has not been ascertained. A vascular casting technique was developed using carmine red dye to measure the vascular volume of the medial collateral ligament (MCL), lateral collateral ligament (LCL), menisci, medial capsule, and infrapatellar fat pad of the rabbit knee joint. Vascular volume determinations were repeated at 4 weeks in a group of anterior cruciate ligament (ACL)-transected animals and in a sham-operated control group. The volume of vessels supplying the MCL was estimated to be 0.22 +/- 0.07 microliter (mean +/- S.E.M.), the LCL volume was 0.25 +/- 0.05 microliter, the medial meniscus volume was 0.19 +/- 0.03 microliter, the lateral meniscus volume was 0.40 +/- 0.08 microliter, the medial capsule volume was 0.14 +/- 0.05 microliter, and the infrapatellar fat pad volume was 1.90 +/- 0.62 microliters. Following ACL transection, angiogenesis was found to occur in the MCL only. All other tissue vascularities were not significantly different from sham-operated controls. A quantifiable method for measuring vascular volume of knee joint tissues has been described. Joint instability stimulates angiogenesis in the ipsilateral MCL; however, the absence of angiogenic activity in other articular tissues might help explain the lack of posttraumatic healing associated with these joints.

Animals↗
PubMed1998

Noninvasive measurement of aortic pressure waveform by ultrasound.

At present, the aortic pressure (Pa) waveform can only be measured invasively. In this paper, we describe a new noninvasive method of measuring Pa. The aortic diameter (Da) pulse waveform was measured noninvasively from the suprasternal fossa using an echo-tracking system that was applied to the anterior and posterior aortic wall echoes. To eliminate viscoelastic distortion, the measured Da was converted to an estimate of Pa, named P beta, using the stiffness parameter beta, which revealed the viscoelastic relationship between the vessel diameter and its internal pressure. P beta was then compared with the Pa pattern that was measured directly. Eight patients with ischemic heart disease who had undergone cardiac catheterization were examined by this method. Results showed that (1) the Da and Pa waveforms were similar; (2) the P beta waveform resembled the Pa waveform more closely than did the Da waveforms for a single cardiac cycle (r = 0.970); and (3) in particular, P beta resembled Pa most closely during the upslope phase of the ejection period (r = 0.996). Our results suggest that the Pa waveform can be accurately estimated from noninvasive measurements by this method.

Adult↗