[Recanalization procedure of the common femoral vein following iatrogenic femoral chronic occlusion: 3 cases]. / Recanalisation veineuse des membres inférieurs sur occlusion fémorale chronique iatrogène : à propos de 3 cas.

Common femoral vein occlusion (CFVO) is frequently found in patients with chronic venous insufficiency. The iatrogenic form, secondary to either central catheter or surgery, is very rare but highly symptomatic. Classical compression therapy barely improves the clinical status of these patients, making them suitable candidates for an interventional procedure for venous recanalization. METHODS: We report here three consecutive cases of iatrogenic CFVO referred to our outpatient clinic because the disease had an impact on daily life activities. We detail the recanalization procedure, the Doppler control and the short-term outcome. RESULTS: In each case, endovascular recanalization required rigid material (rigid guide or Colapinto needle) to cross the fibrous adhesions before angioplasty could be performed with stenting. The procedure required two attempts in each case, underlining its complexity, but eventually enabled effective recanalization. No major complication occurred per- or post-procedure. One month later, a duplex Doppler control confirmed the permeability of the common femoral vein. The patients had experienced rapid and significant symptom improvement. CONCLUSION: Patients suffering from severe chronic venous insufficiency caused by iatrogenic CFVO can benefit from endovascular recanalization. Although these procedures may be complex due to the extensive fibrosis at the Scarpa and require specialized equipment, no major complications were observed. Patency of the recanalization persisted at least one month after the procedure. Symptom relief was good.

[Distal revascularization in diabetic patients with chronic limb ischemia]. / La revascularisation distale des diabétiques en ischémie critique.

Diabetes mellitus is an independent risk factor for peripheral artery disease. Life expectancy is 41 months for diabetic patients with an ischemic ulcer. The characteristics of diabetic arteriopathy make its treatment more difficult than in non-diabetic patients. Few data are available about the surgical treatment of arteriopathy in diabetic patients (including angioplasty or bypass), especially in case of distal arteriopathy. The choice of the procedure depends on multiple factors such as the disease localization, its extent, distal blood flow and vascular disease-related surgical risk. The principal aim of revascularisation is to restore direct flow to the foot in order to ensure wound healing and limb salvage. With percutaneous endoluminal angioplasty, limb salvage can be achieved in more than 80% of patients at 1-3 years. The percutaneous procedure is less invasive than open surgery, there are fewer complications, and morbidity and mortality rates are reduced; moreover, a second procedure remains possible in the future. With bypass surgery, the rate of limb salvage exceeds 80% at five years. Nevertheless, peri-operative mortality reaches 3% and arterial anatomy, patient-related risks factors or venous graft availability may be limitations. New endovascular techniques especially designed for the distal arteries of the lower limbs enable very distal revascularization with morbidity and mortality rates lower than with surgery.

The relation of the peak Doppler E-wave to peak mitral annulus velocity ratio to diastolic function.

Previous observations (Garcia et al. 1998; Sohn et al. 1997; Nagueh et al. 1997) indicate that mitral annulus velocity may be viewed as a "load-independent" index of filling and that wedge pressure is linearly related to the transmitral flow velocity (V(E)) to mitral annulus velocity (V(MA)) ratio (V(E)/V(MA)) measured at maximum velocity. In healthy subjects, the mean value observed for [V(E)](max)/[V(MA)](max) was 1:0.23 approximately 4. No prior physiologic or physical explanation for the basis of, or for the magnitude of, the ratio has been proposed. We propose a physiologic, model-based, quantitative explanation for these observations and test our simplified model's prediction in an invasive (n = 30) and noninvasive (n = 34) test groups of subjects. The simplified geometric model is based on the known constant volume (within a few percentage points) attribute of the four-chambered heart. Accordingly, left-atrial and left-ventricular volumes reciprocate so that their sum is constant throughout the cardiac cycle. The model predicts that: 1. the ratio (V(E)/V(MA)) is a constant approximately 3 in healthy hearts; and 2. V(E)/V(MA) should be linearly proportional to left ventricular end-diastolic pressure (LVEDP). Model prediction was tested using V(E) and V(MA) echocardiographic data from 34 subjects (noninvasive group), and simultaneous echocardiographic and high-fidelity hemodynamic (LVEDP) data in 30 subjects (invasive group). Excellent agreement was observed between model prediction and observed data. For the noninvasive (healthy) group, [V(E)](max)/[V(MA)](max) = 4.20 +/- 1.11. For the invasive group, [V(E)](max)/[V(MA)](max) was observed to be linearly related to LVEDP, [V(E)](max)/[V(MA)](max) = 0.19 (LVEDP) + 1.54, r = 0.92. Hence, [V(E)](max)/[V(MA)](max) is a legitimate flow-derived index of diastolic function because it is a derivable consequence of the heart's constant-volume pump attribute.

Cloning and expression of cDNAs encoding two enzymes of the MEP pathway in Catharanthus roseus.

Two periwinkle cDNAs (crdxr and crmecs) encoding enzymes of the non-mevalonate terpenoid pathway were characterized using reverse transcription-PCR strategy based on the design of degenerated oligonucleotides. The deduced amino acid sequence of crdxr is homologue to 1-deoxy-D-xylulose 5-phosphate reductoisomerases. Crmecs represents the first plant cDNA encoding a protein similar to the 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase from Escherichia coli. Expression of crdxr and crmecs genes was up-regulated in periwinkle cells producing monoterpenoid indole alkaloids. Involvement of the 2C-methyl-D-erythritol 4-phosphate pathway in alkaloid biosynthesis is discussed.

Unsolved problems in diastole.

It is now recognized that a sizable portion of patients who exhibit symptoms of congestive heart failure have relatively well-preserved systolic function, but have significantly elevated LV filling pressures. This syndrome, termed "diastolic heart failure," is associated with various conditions such as aging, anatomic abnormalities, hypertension, ischemic disease, tachycardia, and atrial fibrillation. Advances in the proper medical and surgical management of these patients will depend on the continued delineation of the basic physiologic mechanisms that account for normal and pathologic cardiac diastolic function. This goal can only be achieved by the integration of information acquired from basic science investigations conducted in vitro and in vivo, mathematic modeling simulation studies, and prospective, community-based investigations that characterize the incidence, prevalence, and natural history of the disease. In addition, randomized clinical trials will be needed to determine the optimal treatment strategies for this group of patients--strategy choices undoubtably complicated by a disease whose treatment is influenced to a large extent by its origin. The future therapies evaluated in these randomized clinical trials will most likely range from medical therapies that target either the heart directly or the peripheral vascular system, to surgical interventions such as direct myocardial revascularization, to gene therapy. Finally, it is worth mentioning one more unresolved issue that is of general practical concern not only to the physiologist studying diastolic function, but also to the clinician: whether or not it is even feasible to develop a single, sensitive, specific, clinically relevant index of diastolic function that is free from the contaminating influences of rate, contractility, and load. As observed by Glantz 20 years ago, developing indexes with the hope that one might fully delineate the left ventricle's diastolic properties, rather than concentrating on discovering the physiologic significance of such indexes, is probably counterproductive. More recently, in a related article, Slinker implied that an operational definition of any aspect of cardiac function must allow for the measurement of that function over an adequate range of essential variables. Therefore, as previously mentioned, the physiologist studying cardiac function has the daunting task of trying to understand, in a precise way, how the processes and mechanisms of the various phases of the cardiac cycle couple together to produce either a normal or abnormal functioning heart. It seems clear that because of the complex weave of factors that control overall cardiac diastolic function, the derivation of any single index that adequately describes LV diastolic function in vivo may not be possible.

Estrogen increases hyperemic microvascular blood flow velocity in postmenopausal women.

BACKGROUND: Epidemiologic studies suggest that estrogen replacement therapy (ERT) is protective against vascular disease. ERT confers this benefit by lowering lipid levels and improving arterial function. However, its effect on the microvasculature in vivo is unknown. Thus the purposes of this study were to evaluate effect of estrogen status on the hyperemic response of the microvasculature in vivo in postmenopausal women and to compare the hyperemic response of the microvasculature in postmenopausal women taking ERT with that of premenopausal women. METHODS: We measured forearm microvasculature flow velocity by using a laser Doppler in a cross section of 64 healthy premenopausal and postmenopausal women 23 to 72 years old. Microvasculature blood flow velocity was measured at baseline. throughout 2 minutes of ischemia, and immediately after the ischemic period was terminated (i.e., during the peak hyperemic response). RESULTS: The peak of the hyperemic flow velocity (PHFV) in the postmenopausal women who were taking long-term ERT at usual doses was greater than that of postmenopausal women who were not currently taking ERT (p < .0001). Moreover, the PHFV of postmenopausal women taking ERT was similar to that of premenopausal women. Multivariate regression analysis showed estrogen status and baseline flow velocity to be independent predictors of PHFV. CONCLUSIONS: Current, long-term ERT at usual replacement doses is associated with improved microvascular responses in postmenopausal women, which may explain some of its beneficial vascular effects.

RGS4 causes increased mortality and reduced cardiac hypertrophy in response to pressure overload.

RGS family members are GTPase-activating proteins (GAPs) for heterotrimeric G proteins. There is evidence that altered RGS gene expression may contribute to the pathogenesis of cardiac hypertrophy and failure. We investigated the ability of RGS4 to modulate cardiac physiology using a transgenic mouse model. Overexpression of RGS4 in postnatal ventricular tissue did not affect cardiac morphology or basal cardiac function, but markedly compromised the ability of the heart to adapt to transverse aortic constriction (TAC). In contrast to wild-type mice, the transgenic animals developed significantly reduced ventricular hypertrophy in response to pressure overload and also did not exhibit induction of the cardiac "fetal" gene program. TAC of the transgenic mice caused a rapid decompensation in most animals characterized by left ventricular dilatation, depressed systolic function, and increased postoperative mortality when compared with nontransgenic littermates. These results implicate RGS proteins as a crucial component of the signaling pathway involved in both the cardiac response to acute ventricular pressure overload and the cardiac hypertrophic program.

Plasma lipoprotein distribution and lipid transfer activities in patients with type IIb hyperlipidemia treated with simvastatin.

The aim of the present study was to search in type IIb hyperlipidemic patients for putative concomitant effects of simvastatin on the physicochemical characteristics of low density lipoproteins (LDL) and high density lipoproteins (HDL), as well as on the activities of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) that were determined in both endogenous lipoprotein-dependent and endogenous lipoprotein-independent assays. In a double-blind, randomized trial, patients received either placebo (one tablet/day; n = 12) or simvastatin (20 mg/day; n = 12) for a period of 8 weeks after a 5-week run-in period. Simvastatin, unlike placebo, reduced the lipid and apolipoprotein B contents of the most abundant LDL-1, LDL-2, and LDL-3 subfractions without inducing significant changes in the overall size distribution of LDL and HDL. Whereas simvastatin significantly increased PLTP activity in an endogenous lipoprotein-dependent assay (P < 0.01), no variation was observed in a lipoprotein-independent assay. Simvastatin significantly decreased plasma CETP activity in an endogenous lipoprotein-dependent assay (P < 0.01), and the reduction in plasma cholesteryl ester transfer rates was explained by a 16% drop in CETP mass concentration (P < 0.01). In contrast, the specific activity of CETP was unaffected by the simvastatin treatment reflecting at least in part the lack of significant alteration in plasma triglyceride-rich lipoprotein acceptors. The simvastatin-induced changes in plasma CETP mass levels correlated positively with changes in plasma CETP activity (r = 0.483, P = 0.0561), in total cholesterol levels (r = 0.769; P < 0.01), and in LDL-cholesterol levels (r = 0.736; P < 0.01). Whereas the observations suggest that simvastatin might exert concomitant beneficial effects on plasma CETP and LDL levels, neither plasma cholesteryl ester transfer activity nor plasma phospholipid transfer activity appeared as the main determinants of the LDL and HDL distribution profiles in type IIb hyperlipidemic patients.

Reversal of hypocalcemia and decreased afterload in sepsis. Effect on myocardial systolic and diastolic function.

Sepsis is a major cause of death in intensive care units. Clinically, sepsis induces a number of physiologic and metabolic abnormalities, including decreased myocardial contractility and decreased plasma ionized calcium. There is debate about the proper therapy of hypocalcemia in sepsis because calcium administration may worsen cell function by causing intracellular Ca2+ overload. We investigated the effect of Ca2+ administration on myocardial systolic and diastolic function in an extensively utilized rat model of sepsis, i.e., the cecal ligation and puncture model (CLP). Approximately 24 h after CLP or sham surgery, rats were anesthetized and myocardial function assessed in vivo by a left ventricular Millar catheter and simultaneous two-dimensional guided M-mode echocardiography. Septic rats had a 28% decrease in peak left ventricular developed pressure, a 30% decrease in +dP/ dt, and a 23% decrease in -dP/dt (p < 0.05). Plasma ionized Ca2+ was decreased in septic compared with that in sham rats: 4.9 +/- 0.9 and 5.6 +/- 0.01 mg/dl, respectively (p < 0.05). CaCl2 improved both systolic and diastolic function and there was no evidence of adverse effects of Ca2+ even at supraphysiologic levels. Surprisingly, correction of decreased afterload in septic rats, using the pure alpha-agonist phenylephrine, caused normalization of all indices of cardiac contractility, indicating that the presumed decrease in cardiac function was due entirely to an effect of the decreased afterload to "unload" the left ventricle. We conclude that Ca2+ administration is not detrimental to cardiac function in the rat CLP model. Although the rat CLP model is widely utilized and reproduces many of the clinical hallmarks of sepsis, it does not cause intrinsic myocardial depression and, therefore, it may not be an appropriate model to investigate the clinical cardiac dysfunction that occurs in patients with sepsis.

Correlation between direct ESR spectroscopic measurements and electromechanical and biochemical assessments of exogenous free radical injury in isolated rat cardiac myocytes.

Reactive free radical species appear to be involved in the ischemic injury of cardiac muscle, although the mechanisms by which oxygen-derived free radicals affect the heart cell function are not known. In the present study, cultured ventricular myocytes were exposed to an exogenous oxygen radical generating system. The myocyte-enriched, primary cultures were prepared from ventricles of new-born rat heart and exposed to a xanthine/xanthine oxidase (X+XO) system. The transmembrane potentials were recorded with glass microelectrodes. Cell contractions were monitored photometrically. The release of lactate dehydrogenase (LDH) in the medium was analysed. Quantitative measurement and the time course of the radical generation were performed by the electron paramagnetic resonance (EPR) spin trapping technique with the spin trap 5,5-dimethyl-1-pyroline-N-oxide (DMPO). We verified that X and XO alone had no significant functional and biochemical effects. The X+XO system produced a rapid decrease in the action potential amplitude. This effect was accompanied by a strong decrease in contractility and spontaneous rate. The time course of these functional defects were correlated with a progressive efflux of LDH from the cardiomyocytes. Prolonging the exposure to the X+XO system provoked the cessation of the spontaneous beatings and the progressive loss of the resting diastolic potential, together with a near total release of the cellular LDH. The LDH release and the functional depression were both efficiently prevented by catalase. On the contrary, superoxide dismutase (SOD) slowed down but did not protect against the functional and biochemical effects of the free radicals. In comparison, the EPR spectra obtained indicated that the X+XO system was associated with an important generation of superoxide anions but also with a small hydroxyl production. SOD scavenged the superoxide but a small .OH production persisted. Catalase (CAT) did not modify the superoxide generation but decreased the hydroxyl adduct formation. These results suggest that, although the generation of superoxide anions by the X+XO system was higher than the hydroxyl production, the functional injury and enzyme leakage seemed mainly mediated through a hydrogen peroxide-hydroxyl radical pathway. Cultured ventricular myocytes can be thus used as a valuable model to investigate the cellular mechanism of oxidant-induced damage in the heart.

Dependency of contractile reserve on myocardial blood flow: implications for the assessment of myocardial viability with dobutamine stress echocardiography.

BACKGROUND: Contractile reserve, improvement in contractile function during inotropic stimulation, is a proposed marker of viable myocardium. This study was designed to address, in patients with left ventricular dysfunction due to chronic coronary artery disease, whether contractile reserve depends on myocardial blood flow. METHODS AND RESULTS: We studied 19 patients, at rest and during dobutamine, with 2D echocardiography for regional mechanical function and PET for regional myocardial blood flow ([(15)O]water) and oxygen consumption ([11C]acetate). Of 166 myocardial segments, 21 had normal systolic function, 56 were dysfunctional but contractile reserve-positive, and 89 were dysfunctional and contractile reserve-negative. Myocardial blood flow at rest was lower in contractile reserve-negative (0.41+/-0.18 mL x g(-1) x min(-1)) than in contractile reserve-positive (0.50+/-0.22 mL x g(-1) x min(-1)) and normal segments (0.55+/-0.20 mL x g(-1) x min(-1), P<.009). After dobutamine infusion, blood flow increased less in contractile reserve-negative (0.63+/-0.38 mL x g(-1) x min(-1)) than in contractile reserve-positive (1.28+/-0.65 mL x g(-1) x min(-1)) and normal segments (1.93+/-0.83 mL x g(-1) x min(-1), P<.0001). Likewise, myocardial oxygen consumption was lower at rest in contractile reserve-negative (clearance rate of [11C]acetate, 0.043+/-0.012 min(-1)) than in contractile reserve-positive (0.048+/-0.01 min(-1)) and normal segments (0.058+/-0.008 min(-1), P<.02). Myocardial oxygen consumption with dobutamine increased less in contractile reserve-negative (0.060+/-0.013 min(-1)) than in contractile reserve-positive (0.077+/-0.016 min(-1)) and normal segments (0.092+/-0.024 min(-1), P<.0001). Of segments defined as viable by PET, 54% were contractile reserve-negative and exhibited lower blood flow with dobutamine (0.72+/-0.36 mL x g(-1) x min(-1)) than with viable, contractile reserve-positive segments (1.29+/-0.70 mL x g(-1) x min(-1), P<.0001). CONCLUSIONS: Contractile reserve depends, in part, on the level of myocardial blood flow at rest and during inotropic stimulation.

Postextrasystolic left ventricular isovolumic pressure decay is not monoexponential.

OBJECTIVE: The relationship between the left ventricular (LV) relaxation time constant and early diastolic filling is not fully defined. This study provides additional evidence that LV isovolumic pressure fall in the normal intact heart in response to certain interventions is not adequately described by a model of monoexponential decay and that its relationship to filling is complex. METHODS AND RESULTS: To gain further insight into the relationship between LV relaxation and early rapid filling we measured LV isovolumic relaxation rate, peak early filling velocity (E), LV volumes, and transmitral pressures at baseline and in the first postextrasystolic beat after a short-coupled extrasystole in 9 anesthetized dogs. Postextrasystolic isovolumic relaxation rate was slowed as measured by 3 commonly used time constants, while E was increased 32%. LV contractility and peak pressure were also increased, while LV end-systolic volume was decreased. LV minimum pressure was deceased, while the early diastolic transmitral pressure gradient was increased. Although all relaxation time constants measured over the entire isovolumic relaxation phase indicated slowed relaxation, direct measurement of isovolumic relaxation time indicated no change in relaxation rate. Calculation of the time constants and direct measurement of isovolumic relaxation time during early isovolumic pressure decay indicated slowed postextrasystolic pressure decay rate compared with baseline, while calculation of time constants and direct measurement of isovolumic relaxation time during late isovolumic relaxation indicated augmented postextrasystolic pressure decay rate versus baseline. CONCLUSIONS: This non-exponential behavior of LV isovolumic pressure decay in postextrasystolic beats after short-coupled extrasystoles provides further evidence that the relationship that exists between ventricular relaxation and early filling is not simple. The results are interpreted in terms of current theoretical formulations that attribute control of myocardial relaxation to the interaction between inactivation-dependent and load-dependent mechanisms.

Periodicity in the growth and shedding of hair.

Ten men, with or without alopecia, were observed for a period of between 8 and 14 years using phototrichograms on a precisely located zone on the vertex of the scalp. Among the various parameters observed, we chose the percentage of hairs in telogen as the criterion for assessment of hair shedding. Mathematical analysis of the variations in this telogen percentage was carried out for each individual subject and for the whole group, as represented by the population mean (or the 'average subject'). This analysis demonstrated the existence of overall annual periodicity, manifested by a maximal proportion of telogen hairs at the end of summer and the beginning of autumn. Some subjects also exhibited a periodicity approximately corresponding to two annual peaks. In those subjects with a very low proportion of hairs in telogen, no periodicity was demonstrated. In another group of subjects, it has been shown that the variations in telogen percentage reflect those observed in hair shedding, assessed in a standardized manner. Periodicity of the telogen percentage, and hence of hair fall, is not independent of climatic factors (sunshine hours), and these must be taken into account when assessing the treatment or prevention of hair loss.

Anatomically and physiologically based reference level for measurement of intracardiac pressures.

BACKGROUND: Many reference levels have been proposed for the measurement of intracardiac pressures, but none have met with universal acceptance. In the first part of our study, we evaluated 10 cardiologists' understanding of how hydrostatic pressure influences intracardiac pressures as measured with fluid-filled catheters. In the second part, we proposed and validated a new zero level (H): the uppermost blood level in the left ventricular (LV) chamber relative to the anterior chest wall for a patient in the supine position. A comparison was made of LV minimum diastolic pressure measured by reference to H versus measurements made with the zero level at midchest. METHODS AND RESULTS: Using two-dimensional echocardiography, we determined H in the LVs of seven normal patients (five male, two female; age, 49 +/- 9 years) undergoing routine cardiac catheterization. H was determined from a left parasternal short-axis view and calculated as the average distance between end diastole and end systole of the endocardium of the uppermost segment of the LV anterior wall below the fourth or fifth intercostal space of the left sternal border on the anterior surface of the chest wall, with the patient in the supine position. A micromanometer/fluid-filled lumen catheter was then positioned in the LV, and we compared the micromanometer LV minimum pressure (LVPmin) obtained when the reference fluid-filled transducer was aligned at midchest with the LVPmin obtained when the reference fluid-filled transducer was aligned at H. LVPmin referenced to a midchest fluid-filled external transducer was measured as 5.1 +/- 1.6 mm Hg (range, 2.4 to 7.2 mm Hg) versus -0.6 +/- 0.6 mm Hg (range, -1.6 to 0.4 mm Hg) when referenced to H (P < .001). A significant linear relation was found to exist between patient anterior-posterior chest diameter and the magnitude of hydrostatic pressure influences related to pressure referenced at midchest (r = .88; P < .01). CONCLUSIONS: External fluid-filled transducers should be used with the goal of removing hydrostatic pressure and other influences so that the presence of subatmospheric pressure during diastole in any of the cardiac chambers is accurately measured. To achieve this goal, intracardiac pressure should be referenced to an external fluid-filled transducer aligned with the uppermost blood level in the chamber in which pressure is to be measured. The current practice of referencing the zero level of LV diastolic pressure to an external fluid-filled transducer positioned at the midchest level results in systematic overestimation due to hydrostatic effects and produces physiologically significant error in the measurement of diastolic intracardiac pressure.

Ageing and hair cycles.

The phototrichogram is a non-invasive technique by which, on the same precise area of the scalp, each individual hair may be identified, and its current growth phase established. This technique was used to study the duration of hair cycles in 10 male subjects, balding and non-balding, by observations at monthly intervals over a period of 8-14 years. The accumulated data served to characterize the effects of ageing in these subjects: a reduction in the duration of hair growth and in the diameter of hair shafts, most evident in the thickest hairs, and a prolongation of the interval separating the loss of a hair in telogen and the emergence of a replacement hair in anagen. These various aspects of ageing of scalp hair contribute to its progressive overall impoverishment. They resemble those observed in the course of male-pattern balding, although their development is less marked.

Delineation of determinants of left ventricular early filling. Saline versus blood infusion.

BACKGROUND: Left atrial pressure (LAP) is often believed to play a dominant role in the determination of left ventricular (LV) early diastolic filling. In a previous study we found no significant relation between LAP and LV early filling velocity (E) but found instead a relation between E and two determinants of LV myocardial shortening (contractility and afterload). To determine if such disparate results may be related to the data ranges of the independent variables in a given population of animals, we took advantage of the differential hemodynamic effects of two modes of volume expansion: saline and whole blood. METHODS AND RESULTS: Eighteen closed-chest anesthetized dogs were instrumented with micromanometers for measurement of LV, left atrial, and aortic pressures. LV volumes were obtained with use of contrast ventriculography, pressures by micromanometry, and transmitral flow-velocity by Doppler echocardiography. After obtaining baseline measurements, group 1 (n = 9) received rapid infusion of 500 to 650 mL of saline over 10 minutes, and group 2 (n = 9) received the same volume infusion of whole blood. In terms of two known determinants of E, infusion of saline resulted in a significant increase in LAP at the moment of mitral valve opening (X1) (1.5 +/- 0.9 to 5.7 +/- 1.4 mm Hg; P < .05) and a moderate decrease in the pressure decay rate during isovolumic relaxation (tau 1/2) (22.9 +/- 2.4 to 26.3 +/- 3.5 milliseconds; P < .05). When these two factors were entered together into a multiple regression analysis with E as the dependent variable, the overall correlation was found to be significant (R = .722; P < .008), with both independent variables contributing significantly to the relation. When factors related to myocardial shortening (afterload and contractility) were added to this relation, they did not significantly improve the prediction of E. Like saline, whole blood infusion augmented X1 (1.6 +/- 2.4 to 8.8 +/- 3.2 mm Hg; P < .05) and tau 1/2 (21.5 +/- 2.6 to 32.0 +/- 6.3 milliseconds; P < .05) but also significantly increased LV afterload as measured by aortic diastolic pressure (91 +/- 10 to 110 +/- 12 mm Hg; P < .05). Multiple regression analysis of X1 and tau 1/2 with E again revealed a significant relation (R = .761; P < .002), with both independent variables contributing significantly to the relation. However, in this case, addition of contractility and afterload to the regression significantly improved the relation (R = .909; P < .001), with all four independent variables now contributing significantly to the prediction of E. CONCLUSIONS: Combined with our previous results, this study indicates the degree to which experimental methods can have an impact on the delineation of the determinants of a phenomenon as complex as LV early diastolic filling. Which independent variables emerge as primary determinants can be strongly influenced by the experimenter's choice of experimental design and manipulations. Specifically, experiments using volume infusion to delineate the responses of the cardiovascular system to variations in loading must allow for the hemodynamic changes that are inherent in the choice of infusate and infusion technique, especially when those interventions may significantly alter blood oxygen-carrying capacity and, in turn, differentially modify factors that affect the magnitude of the early diastolic transmitral pressure gradient.

Hair cycle and alopecia.

Male pattern alopecia is the outcome of profound modifications in the duration, succession and frequency of hair cycles. These phenomena were studied by phototrichogram in 10 male subjects, with or without alopecia, over a period of 15 years. Almost 10,000 hair cycles were accounted for, yielding a detailed picture of the alopecia condition: (1) A decrease in the duration of anagen for a certain proportion of hairs, a proportion which increases in size, the more advanced the alopecia; the result of this premature transformation from anagen to telogen is an increase in the rate of hair loss. (2) A parallel decline in hair diameter. (3) Longer latency periods between the fall of a hair and the onset of regrowth, leading to a reduction in the number of hairs present on the scalp surface. The shorter finer hairs are absent more frequently and absent for longer periods and this contributes to the effect of alopecia.

Factors related to end-systolic volume are important determinants of peak early diastolic transmitral flow velocity.

BACKGROUND: Three important determinants of left ventricular (LV) peak early diastolic filling rate, which is related directly to the magnitude of the transmitral pressure difference, are the rate of LV isovolumic pressure fall (T1/2), left atrial (LA) pressure at mitral valve opening (X1), and end-systolic volume (ESV). METHODS AND RESULTS: To delineate the relative degrees to which these factors contribute to the magnitude of peak early diastolic filling rate, we measured LA and regional intra-LV pressures with micromanometers, LV volume with contrast angiography, and peak transmitral flow velocity (E) with transesophageal Doppler echocardiography in 16 anesthetized closed-chest dogs. E did not correlate significantly with either X1 (r = -0.255) or T1/2 (r = -0.281). Multivariate analysis, with E entered as the dependent variable and X1 and T1/2 as independent variables, also failed to reach significance (R = 0.310). E correlated significantly with ESV (r = -0.633, p less than 0.009). Using multivariate analysis, the major determinants of ESV were found to be LV contractility (+dP/dt), afterload (aortic diastolic pressure, AOdias), and preload (end-diastolic volume, EDV) (R = 0.848, p less than 0.001). E correlated significantly with two of the determinants of ESV (+dP/dt and AOdias) (R = 0.906, p less than 0.001); however, the addition of EDV did not significantly improve the multivariate relation (R = 0.911). To determine whether X1 or T1/2 would add significantly to the above multivariate relation, these factors were entered individually along with +dP/dt and AOdias as third independent variables. Neither the addition of X1 (R = 0.906) or T1/2 (R = 0.926) resulted in a significant improvement in the prediction of E. CONCLUSIONS: Our observations confirm the importance of factors related to ESV as important determinants of early diastolic filling. These relations suggest that the process of early diastolic function is intimately related to systolic function.

Polyunsaturated fatty acids in cultured cardiomyocytes: effect on physiology and beta-adrenoceptor function.

This study was carried out to investigate the influence of the membrane fatty acid composition on the basal electrical and contractile activities and the response to beta-adrenergic stimulation of rat cardiac muscle cells in culture. Cells were grown for 3 days in a conventional serum culture medium and then incubated for 24 h in synthetic media containing either n-6 or n-3 as the sole source of polyunsaturated fatty acids (PUFA). The n-6/n-3 ratio in the phospholipids was 0.9 in the n-3 cells and 13.1 in the n-6 cells compared with 6.3 in controls cells. Such modifications did not alter action potentials and the main parameters related to contraction, although shortening was slightly accelerated in the n-6 cells. On the other hand, the positive chronotropic effect induced by isoproterenol was more pronounced (P less than 0.01) in n-3 cells than in n-6 cells. In addition, isoproterenol caused a decrease in contraction duration and in shortening and relaxation time that was less pronounced in n-6 than in control cells (P less than 0.01, P less than 0.01 and P less than 0.05, respectively). These results suggest that the PUFA balance in the phospholipids may contribute to modulate the cardiac adrenergic receptor system but not the membrane properties related to electro-mechanical functions.