Ivabradine reduces myocardial stunning in patients with exercise-inducible ischaemia.

Ivabradine is an effective treatment for angina in patients with stable coronary artery disease (CAD) and for heart failure. Experiments in a canine model have shown that ivabradine reduces both acute left ventricular (LV) dysfunction and post-ischaemic stunning. Aim of this study was to investigate the effect of ivabradine on LV dysfunction and stunning in patients with CAD and exercise-inducible ischaemia. Fifteen patients with ejection fraction >40 % and heart rate >70 bpm were enrolled. After pharmacologic washout, echocardiography was performed at rest, at peak treadmill exercise and during recovery until return to baseline. After 2 weeks of ivabradine (7.5 mg bid) stress echocardiography was repeated at the same workload achieved during washout. Peak global and segmental (ischaemic vs. remote normal segments) LV longitudinal strain (LS) was assessed by 2D speckle tracking analysis. At washout, LS was significantly impaired in ischaemic compared to remote segments at peak stress and for several minutes during recovery. After ivabradine a smaller, albeit still significant, impairment of LS in ischaemic segments was observed at peak whilst no difference with remote segments was present during recovery. Furthermore, the average global LS value improved significantly after treatment. In conclusion, ivabradine reduces both acute LV dysfunction and stunning in patients with CAD and exercise-inducible ischaemia. We hypothesise that this mechanism might contribute to reduce chronic LV dysfunction in patients with CAD. In this setting the drug might limit the development of hibernating myocardium which is believed to result from repeated episodes of ischaemia and stunning.

Dopamine release from nigral transplants visualized in vivo in a Parkinson's patient.

Synaptic dopamine release from embryonic nigral transplants has been monitored in the striatum of a patient with Parkinson's disease using [11C]-raclopride positron emission tomography to measure dopamine D2 receptor occupancy by the endogenous transmitter. In this patient, who had received a transplant in the right putamen 10 years earlier, grafts had restored both basal and drug-induced dopamine release to normal levels. This was associated with sustained, marked clinical benefit and normalized levels of dopamine storage in the grafted putamen. Despite an ongoing disease process, grafted neurons can thus continue for a decade to store and release dopamine and give rise to substantial symptomatic relief.

Three new small nucleolar RNAs that are psoralen cross-linked in vivo to unique regions of pre-rRNA.

We have recently described three novel human small nucleolar RNA species with unique nucleotide sequences, which were named E1, E2, and E3. The present article describes specific psoralen photocross-linking in whole HeLa cells of E1, E2, and E3 RNAs to nucleolar pre-rRNA. These small RNAs were cross-linked to different sections of pre-rRNA. E1 RNA was cross-linked to two segments of nucleolar pre-rRNA; one was within residues 697 to 1163 of the 5' external transcribed spacer, and the other one was between nucleotides 664 and 1021 of the 18S rRNA sequence. E2 RNA was cross-linked to a region within residues 3282 to 3667 of the 28S rRNA sequence. E3 RNA was cross-linked to a sequence between positions 1021 and 1639 of the 18S rRNA sequence. Primer extension analysis located psoralen adducts in E1, E2, and E3 RNAs that were enriched in high-molecular-weight fractions of nucleolar RNA. Some of these psoralen adducts might be cross-links of E1, E2, and E3 RNAs to large nucleolar RNA. Antisense oligodeoxynucleotide-targeted RNase H digestion of nucleolar extracts revealed accessible segments in these three small RNAs. The accessible regions were within nucleotide positions 106 to 130 of E1 RNA, positions 24 to 48 and 42 to 66 of E2 RNA, and positions 7 to 16 and about 116 to 122 of E3 RNA. Some of the molecules of these small nucleolar RNAs sedimented as if associated with larger structures when both nondenatured RNA and a nucleolar extract were analyzed.

alpha-adrenergic coronary vasoconstriction and myocardial ischemia in humans.

The use of quantitative coronary angiography, combined with Doppler and PET, has recently been directed at the study of alpha-adrenergic coronary vasomotion in humans. Confirming prior animal experiments, there is no evidence of alpha-adrenergic coronary constrictor tone at rest. Again confirming prior experiments, responses to alpha-adrenoceptor activation are augmented in the presence of coronary endothelial dysfunction and atherosclerosis, involving both alpha(1)- and alpha(2)-adrenoceptors in epicardial conduit arteries and microvessels. Such augmented alpha-adrenergic coronary constriction is observed during exercise and coronary interventions, and it is powerful enough to induce myocardial ischemia and limit myocardial function. Recent studies indicate a genetic determination of alpha(2)-adrenergic coronary constriction.

Effect of troglitazone on the desaturases in a rat model of insulin-resistance induced by a sucrose-rich diet.

A sucrose-rich diet generates time-dependent metabolic disorders similar to those found in diabetes type 2. After 8 month (mo) this diet evoked in the rat an increase of blood glucose, free fatty acids (FFA) and triacylycerides (TG) without insulin modification, an interruption of liver stearoyl-CoA desaturase-1 (SCD-1) mRNA and activity increase found at 6 mo, and an enhacement of Delta6 and Delta5 desaturase mRNA and Delta6 activity. We found that the administration of troglitazone (TRO), a peroxisome-proliferator-activated receptors gamma (PPAR-gamma) agonist, for 2 mo normalized plasma FFA, TG, and glucose without altering the insulinemia. It depressed liver SCD-1 mRNA in both control and sucrose-fed rats, decreasing the 18:1n-9/18:0 ratio in serum and liver lipids, and eliminated the increasing effect on mRNA and activity of Delta6 and Delta5 desaturases. These findings evidence again that desaturases are not affected through an insulin resistant effect evoked by the sucrose-rich diet and TRO recovers the altered metabolic plasma parameters as it corresponds to a PPAR-gamma agonist, but its effect on hepatic desaturases can not be attributed to a direct action on liver by PPAR-gamma, insulin, and even by an insulin sensitizing mechanism, suggesting it would be evoked indirectly through hepatic PPAR-alpha deactivation induced by the FFA decrease.

Reduced cardiovascular sympathetic excitatory responses during iloprost infusion in conscious dogs.

STUDY OBJECTIVE: The aim was to determine the effects of the stable prostacyclin analogue iloprost (ZK 36374) on systemic haemodynamics and on cardiovascular neural control. DESIGN: The buffering effect was examined of intravenous and intracoronary iloprost infusion on the excitatory sympathetic reflexes elicited from the heart by (1) intracoronary injections of bradykinin and (2) transient coronary artery occlusion. SUBJECTS: 22 conscious mongrel dogs of either sex, weight 20-25 kg, were used. MEASUREMENTS AND MAIN RESULTS: ECG, systemic arterial pressure, left atrial pressure, and left ventricular pressure, and contractility (dP/dt) were continuously monitored for the duration of the experiments. Iloprost infusion reduced left ventricular pressure, mean arterial pressure, and dP/dt without causing significant changes in heart rate. Transient non-hypertensive coronary artery occlusion increased heart rate and depressed contractility. During intravenous iloprost infusion, coronary artery occlusion no longer elicited an increase in heart rate, while left ventricular dP/dt was more drastically reduced. This pattern of response was not substantially modified by beta adrenergic blockade, whereas the blockade of muscarinic receptors with atropine was accompanied by hypotension and a greater reduction of dP/dt. The observation of a reduced pressor response to the intracoronary injections of bradykinin during iloprost administration further indicated a restraining effect of iloprost on the sympathetic reflexes elicited from the heart. CONCLUSIONS: The data suggest the hypothesis that the protective effects on the ischaemic myocardium observed with iloprost infusions may arise not only from its vasodilator and antiplatelet properties, but also from its capacity to blunt excitatory sympathetic reflexes.

Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans.

OBJECTIVE: Absolute myocardial blood flow (MBF) is not well-defined in large normal populations, and appears to be heterogeneous in both humans and animals. These factors contribute to the difficulties in defining resting MBF to hibernating myocardium. We therefore assessed absolute baseline and hyperemic MBF in a large population of normal humans. METHODS: MBF was quantified by positron emission tomography with oxygen-15-labeled water at baseline and during hyperemia induced by either adenosine or dipyridamole in 131 men and 38 women, aged 21-86 (mean 46+/-12) years. MBF was corrected for workload using the rate-pressure product (RPP). RESULTS: Uncorrected baseline MBF ranged from 0.590 to 2.050 (mean 0.985+/-0.230) ml/min/g (coefficient of variation=27%), and corrected MBF from 0.736 to 2.428 (mean 1.330+/-0.316) ml/min/g (coefficient of variation=24%). MBF in the inferior region was significantly (P<0.0001) lower than either the anterior or lateral regions. Baseline MBF in females was significantly (P<0.001) higher than in males. CONCLUSIONS: These results confirm the heterogeneity of MBF in normals and highlight the difficulty in establishing the lower limit of normal MBF.

Effects of verapamil, nifedipine, and dilazep on left ventricular relaxation in the conscious dog.

The cardiac systolic and diastolic effects of the two major calcium blockers, verapamil and nifedipine, were studied and compared with those produced by dilazep, a relatively new vasodilator with calcium blocking properties, in conscious instrumented dogs to avoid the complications of anaesthesia and recent surgery. Mean arterial pressure was reduced by nifedipine and dilazep but not by verapamil, whereas peak left ventricular pressure was reduced only by dilazep and verapamil. Consistent tachycardia occurred, the rate being highest with nifedipine and lowest with dilazep. Left ventricular dP/dt was unaffected by dilazep, reduced by verapamil, and increased by nifedipine; this increase was no longer observed after beta adrenergic blockade. Ventricular relaxation was assessed by calculating the time relaxation constant, tau. Verapamil increased tau significantly only after beta adrenergic blockade, whereas nifedipine and dilazep reduced it both before and after beta adrenergic blockade. These data suggest that reflex beta adrenergic mechanisms may modulate the effects of calcium blockade on both systolic and diastolic performance.

Repetitive myocardial stunning in pigs is associated with the increased expression of inducible and constitutive nitric oxide synthases.

OBJECTIVES: Nitric oxide (NO) has complex effects on myocardial function particularly following ischaemia-reperfusion. The goal of this study was to examine the result of repetitive myocardial stunning on myocardial NO release and expression of inducible (iNOS) and constitutive (eNOS) NO synthases. METHODS AND RESULTS: Propofol anaesthetised pigs underwent ten, 2-min episodes of circumflex artery occlusion (n = 6) or acted as sham operated controls (n = 4). Measurements of segment shortening demonstrated a fall in function in the ischaemic territory to 52.5 +/- 7.3% (mean +/- S.E.M.) of baseline shortening 30 min after the stunning stimulus, recovering to 92 +/- 8.7% 5.5 h later. Function remained stable in sham controls. The change in venous-arterial [NO] between baseline and 6 h reperfusion was found to be significantly different between the two groups (0.2 +/- 0.7 in stunned vs. -4.3 +/- 1.6 microM in shams; P < 0.02). Western blotting and band optical density used to compare tissue from stunned territory (S), non-stunned territory (IC) and sham control animals (SC) demonstrated this was associated with an increase in the expression of both iNOS (S: 93 +/- 13.4, IC: 37 +/- 2.4 and SC: 25 +/- 4 [arbitrary units], P < 0.01 and P = 0.031) and eNOS (S: 104 +/- 7.4, IC; 62.5 +/- 7.4 and SC; 75.7 +/- 0.6, P < 0.03 and P < 0.01) in stunned myocardium. Immunocytochemistry localised iNOS reactivity to vascular smooth muscle cells and cardiomyocytes in stunned tissue and eNOS reactivity to endothelial cells. CONCLUSION: Recovery from repetitive myocardial stunning is associated with the increased expression of both iNOS and eNOS and would be compatible with a protective role for both these enzymes. This finding has possible relevance for both the late window of ischaemic preconditioning and myocardial hibernation.

Assessment of the reproducibility of baseline and hyperemic myocardial blood flow measurements with 15O-labeled water and PET.

UNLABELLED: PET with 15O-labeled water allows noninvasive quantification of myocardial blood flow (MBF) at baseline and during pharmacologically induced hyperemia to assess the coronary vasodilator reserve (CVR = hyperemic/baseline MBF). Despite widespread use of PET, its reproducibility during one study session has not been tested. Intravenous adenosine (Ado), a powerful coronary vasodilator with a very short decay time, is commonly used for the induction of hyperemia. However, it is not known whether Ado can induce tachyphylaxis after short-term repetitive administration. In this study, we aimed to test the reproducibility of PET assessment of CVR during Ado-induced hyperemia. METHODS: In 21 healthy volunteer men, baseline and Ado MBF were measured twice using PET with 15O-labeled water to obtain two CVR assessments within 1 h. RESULTS: There was no significant difference between the two baselines (0.89 +/- 0.14 versus 0.99 +/- 0.15 mL/min/g, mean difference 13% +/- 11%) or between the two hyperemic MBFs (3.51 +/- 0.45 versus 3.83 +/- 0.49 mL/min/g, mean difference 10% +/- 14%), resulting in comparable values of CVR (4.05 +/- 0.75 versus 3.93 +/- 0.72, mean difference 2% +/- 15%). The repeatability coefficient for MBF was 0.17 mL/min/g at baseline and 0.94 mL/min/g during hyperemia. The repeatability coefficient of the rate pressure product (RPP) was lower at baseline (1,304 mm Hg x beat/min) than during hyperemia (3,448 mm Hg x beat/min). CONCLUSION: Repeated measurements of MBF and CVR during the same study session were not significantly different, demonstrating the validity of the technique. The larger variability of hyperemic flow, as indicated by the larger repeatability coefficient, was paralleled by a greater variability of the RPP. This could mean that the greater variability of MBF during stress is more likely due to a variable response to Ado rather than to a measurement error.

Detection and quantification of a very high density lipoprotein in different tissues of Triatoma infestans during the last nymphal and adult stages.

The presence of a very high density lipoprotein (VHDL), an hexameric protein, was explored in different tissues of Triatoma infestans throughout the last nymphal and adult stages, and in egg extracts by Western blot assays. The VHDL was always detected in both, hemolymph and fat body, during the above mentioned stages and it was also observed in the buffer soluble fraction of testis and egg homogenates. An enzyme-linked immunosorbent assay (ELISA) was used to measure the VHDL titer in these tissues. Hemolymph VHDL reaches a maximum value before the last molt, then it abruptly declines in males and females just after emergence, but during adult life it increases again. Fat body VHDL decreases slowly and continuously during the nymph growth reaching a minimum value prior to molting, and in the first week of adult life the values were even two-fold lower; then, it shows a different cycle of accumulation and depletion in males and females. In adult testis the VHDL undergoes a cycle similar to the one observed in male fat body. This protein increases progressively during embryonic development and, at the time of larval hatching it reaches its maximum value. The hexameric protein presents homologies in its N-terminal sequence with storage hexamerins of Diptera, Lepidoptera and Hymenoptera.

Analysis of neural mechanisms accompanying different intensities of dynamic exercise.

The neural mechanisms accompanying dynamic exercise of different intensities were analyzed in dogs and human subjects by means of autoregressive spectral analysis of heart period and arterial pressure variabilities. In the animal experiments, 8 conscious dogs were examined after implanting a solid state pressure gauge in the left ventricle. Animals were examined at rest and during a treadmill run, at 4 km/h, and 0 degrees incline. The experiments were repeated after chronic alpha 1-adrenoreceptor blockade. During the treadmill run, heart rate and systolic left ventricular pressure increased significantly. Simultaneously, the low frequency (LF, 0.1 Hz) component of pulse interval and of systolic pressure variabilities, ie, markers, respectively, of sympathetic modulation of the SA node and of vasomotor activity, increased significantly (evaluated respectively, in normalized and absolute units). After chronic alpha 1-adrenoreceptor blockade, the increase in LF component of systolic pressure variability was prevented, while that observed in R-R interval variability was maintained. Human studies were carried out with either invasive or noninvasive techniques. In the former approach already described, performed in young hypertensive subjects, arterial pressure was recorded with a high fidelity technique. In the second approach applied to young champion swimmers, only the variability of the R-R interval was examined. In both studies, moderate levels of exercise were accompanied by an increase in the LF component of the spectrum: in the case of arterial pressure variability, this increase was detectable both in absolute and normalized units; vice versa, in the case of R-R variability, since physical exercise is accompanied by a marked abatement of the variance, normalized units had to be used in order to evaluate the shift of the sympathovagal balance in favor of sympathetic overactivity.

Prolonged left ventricular dysfunction occurs in patients with coronary artery disease after both dobutamine and exercise induced myocardial ischaemia.

OBJECTIVE: To determine whether pharmacological stress leads to prolonged but reversible left ventricular dysfunction in patients with coronary artery disease, similar to that seen after exercise. DESIGN: A randomised crossover study of recovery time of systolic and diastolic left ventricular function after exercise and dobutamine induced ischaemia. SUBJECTS: 10 patients with stable angina, angiographically proven coronary artery disease, and normal left ventricular function. INTERVENTIONS: Treadmill exercise and dobutamine stress were performed on different days. Quantitative assessment of systolic and diastolic left ventricular function was performed using transthoracic echocardiography at baseline and at regular intervals after each test. RESULTS: Both forms of stress led to prolonged but reversible systolic and diastolic dysfunction. There was no difference in the maximum double product (p = 0.53) or ST depression (p = 0.63) with either form of stress. After exercise, ejection fraction was reduced at 15 and 30 minutes compared with baseline (mean (SEM), -5.6 (1.5)%, p < 0.05; and -6.1 (2.2)%, p < 0. 01), and at 30 and 45 minutes after dobutamine (-10.8 (1.8)% and -5. 5 (1.8)%, both p < 0.01). Regional analysis showed a reduction in the worst affected segment 15 and 30 minutes after exercise (-27.9 (7.2)% and -28.6 (5.7)%, both p < 0.01), and at 30 minutes after dobutamine (-32 (5.3)%, p < 0.01). The isovolumic relaxation period was prolonged 45 minutes after each form of stress (p < 0.05). CONCLUSIONS: In patients with coronary artery disease, dobutamine induced ischaemia results in prolonged reversible left ventricular dysfunction, presumed to be myocardial stunning, similar to that seen after exercise. Dobutamine induced ischaemia could therefore be used to study the pathophysiology of this phenomenon further in patients with coronary artery disease.

Spectral decomposition in multichannel recordings based on multivariate parametric identification.

A method of spectral decomposition in multichannel recordings is proposed, which represents the results of multivariate (MV) parametric identification in terms of classification and quantification of different oscillating mechanisms. For this purpose, a class of MV dynamic adjustment (MDA) models in which a MV autoregressive (MAR) network of causal interactions is fed by uncorrelated autoregressive (AR) processes is defined. Poles relevant to the MAR network closed-loop interactions (cl-poles) and poles relevant to each AR input are disentangled and accordingly classified. The autospectrum of each channel can be divided into partial spectra each relevant to an input. Each partial spectrum is affected by the cl-poles and by the poles of the corresponding input; consequently, it is decomposed into the relevant components by means of the residual method. Therefore, different oscillating mechanisms, even at similar frequencies, are classified by different poles and quantified by the corresponding components. The structure of MDA models is quite flexible and can be adapted to various sets of available signals and a priori hypotheses about the existing interactions; a graphical layout is proposed that emphasizes the oscillation sources and the corresponding closed-loop interactions. Application examples relevant to cardiovascular variability are briefly illustrated.

Neural control of vasomotor tone of large coronary arteries.

In man, the occurrence of constrictions of large coronary arteries accompanied by transient myocardial ischemia is now well established. However, the role of neural factors involved in such coronary artery spasms is still a matter of conjecture. A consistent reduction (9 +/- 2%) of the diameter of the large coronary arteries can be obtained in the conscious dog with alpha-adrenergic receptor stimulation with methoxamine in spite of the concomitant pressor rise (65 +/- 5%). Smaller reductions in coronary diameter can be obtained with electrical efferent sympathetic stimulation in anesthetized dogs. The diameter of a conduit artery such as the aorta can be reduced (5%) by reflex increases in sympathetic efferent activity: therefore it is not unlikely that similar neural influences might be exerted on the coronary tree as well. In normal life, stressful situations, such as emotion or exercise, will be accompanied by a drastic increase in sympathetic drive to the heart, together with a marked increase in coronary flow. The latter will induce an endothelial mediated vasodilation; however the net effect on coronary size of these two potentially opposite mechanisms is as yet unexplored. In the laboratory, intracoronary bradykinin and regional myocardial ischemia initiate a reflex increase in sympathetic activity to the heart; in the clinics acute myocardial ischemia can be accompanied by signs of sympathetic overactivity. The extent to which such increases in sympathetic activity, could play a role in the control of coronary tone and hence in the pathophysiology of coronary artery disease, is still under investigation.

Purification and properties of a small lipid-binding protein from the hemolymph of Triatoma infestans.

A small lipid-binding protein (sLBP) was purified from the hemolymph of the blood-sucking bug Triatoma infestans. Its isolation involved size exclusion-high performance liquid chromatography (HPLC) followed by anion exchange chromatography-HPLC. The molecular weight of the protein, as determined by gel permeation chromatography, was 20 kDa. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) resolved the protein into a single polypeptide with M(r) approximately equal to 16 kDa. The sLBP contains 6% lipids. Diacylglycerols represent the major lipid class, whereas phosphatidyl-choline, phosphatidyl-ethanolamine, free fatty acids and hydrocarbons were found in minor amounts. The amino acid composition indicated a high content of aspartic and glutamic acids and non-polar aliphatic amino acids. The N-terminal sequence did not resemble the sequence of any other previously reported insect hemolymph protein. Far-UV circular dichroism suggested that sLBP adopts a conformation rich in beta-sheet structure. The presence of this protein in hemolymph, fat body and unfertilized eggs was explored throughout the last nymphal and adult stages of the insect by Western blot assays. These assays indicated that sLBP is particularly abundant in hemolymph. A high concentration of sLBP was also detected in the fat body of the nymphs.

Myocardial hibernation vs repetitive stunning in patients.

Myocardial hibernation is a state of persistently impaired left ventricular function in patients with coronary artery disease that was thought to be caused by a chronic reduction in resting myocardial blood flow in a segment subtended by a diseased coronary artery. However, recent studies using positron emission tomography have demonstrated that absolute myocardial blood flow (ml/min/g) to hibernating myocardium is within normal limits in most patients. If resting flow is not reduced, one must therefore suspect an alternative "trigger" for hibernation that is still a consequence of coronary artery disease and ischemia. We suspect that hibernating myocardium may be the result of repetitive myocardial stunning. Myocardial stunning is the reversible contractile dysfunction occurring after a period of myocardial ischemia that persists for a period of time despite the return of blood flow to normal. Myocardial stunning has been demonstrated in humans in the setting of thrombolysis, coronary angioplasty, coronary artery bypass surgery, and coronary artery spasm. Furthermore, stunning has been demonstrated after exercise in patients with coronary artery disease, and recent studies have provided evidence that repetitive episodes of exercise-induced ischemia can lead to cumulative and prolonged left ventricular dysfunction.

Model for the assessment of heart period and arterial pressure variability interactions and of respiration influences.

A model which assesses the closed-loop interaction between heart period (HP) and arterial pressure (AP) variabilities and the influence of respiration on both is applied to evaluate the sources of low frequency (LF approximately 0.1 Hz) and high frequency (HF, respiratory rate approximately 0.25 Hz) in conscious dogs (n = 18) and humans (n = 5). A resonance of AP closed-loop regulation is found to amplify LF oscillations. In dogs, the resonance gain increases slightly during baroreceptor unloading (mild hypotension obtained with nitroglycerine (NTG) i.v. infusion, n = 8) and coronary artery occlusion ((CAO), n = 6), and it is abolished by ganglionic transmission blockade ((ARF), Arfonad i.v. infusion, n = 3). In humans, this gain is considerably increased by passive tilt. Different, possibly central, sources of LF oscillations are also evaluated, finding a strong rhythmic modulation of HP during CAO. At HF, a direct respiratory arrhythmia is dominant in dogs at control, while it is considerably reduced during CAO. On the contrary, in humans, a strong influence of respiration on AP is shown which induces a reflex respiratory arrhythmia. An index of the gain of baroreceptive response, alpha cl, was decreased by NTG and CAO, and virtually abolished by chronic arterial baroreceptive denervation (TABD, n = 4) and ARF.

Immunohistochemical detection of a very high density lipoprotein (VHDL) in ovarian follicles of Triatoma infestans.

The ability of Triatoma infestans ovarian follicles to synthesize a very high-density lipoprotein (VHDL) has been examined by immunohistochemical methods. This kind of lipoprotein can be envisaged as a storage hexameric protein present in the hemolymph of some insect species. VHDL immunoreactivity is observed in oocytes at different stages of maturation. The antigen is present in the oocyte cytoplasm as well as in the follicular epithelial cells. The immunopositive reaction in the apical surface of follicle cells suggests both a VHDL synthesis and a secretion process. Furthermore, VHDL seems to be stored into oocyte in yolk granules. On the contrary, no immunopositive reaction is observed in the intracellular spaces between follicle cells, suggesting that VHDL is not incorporated from hemolymph into the oocyte.

Power spectral density of heart rate variability as an index of sympatho-vagal interaction in normal and hypertensive subjects.

Instantaneous heart rate reflects sympatho-vagal influences on pace-maker activity. Hence computer analysis of heart rate variability might provide a quantitative index of that interaction. The power spectral density (PSD) estimate of heart rate variability was obtained in normal controls and in uncomplicated hypertensives, both at rest and during a non-hypotensive sympathetic stimulus (tilting). In normal controls PSD shows three major peaks of frequencies P1 = 0.07, P2 = 0.12, P3 = 0.25 cycles/beat. P1, which is associated with sympathetic activity, represents only a minor portion of total variability at rest, while becoming predominant with tilting. P2 and P3 are associated with vagal activity, and represent the major part of variability at rest, while they are reduced by tilting. In hypertensive patients PSD is altered, as P1 is already predominant at rest and increases only slightly with tilting. Thus PSD of heart rate variability is capable of detecting an early alteration in sympatho-vagal balance of cardiac control present in uncomplicated hypertension.