Pierre Albaladejo

Angiotensin converting enzyme inhibition prevents the increase in aortic collagen in rats.

Four groups of 4-week-old spontaneously hypertensive rats were treated during 4 months with the angiotensin converting enzyme inhibitor quinapril at 1 mg/kg per day (Q1) or 10 mg/kg per day (Q10), hydralazine at 15 mg/kg per day (H), or placebo (P). In the first set of experiments, blood pressure was measured in conscious rats, and plasma and aortic angiotensin converting enzyme activities were evaluated. In the second set of experiments, histomorphometric parameters of the thoracic aorta were evaluated. Mean blood pressure was lower in the Q10 and H groups (136 +/- 16 and 149 +/- 11 mm Hg) compared with the P group (190 +/- 23 mm Hg) (P < .01). The Q1 group showed mean blood pressure values (171 +/- 15 mm Hg) lower than the P group (P < .05) but significantly higher than the Q10 and H groups (P < .01 and P < .05, respectively). Aortic medial cross-sectional area was significantly lower in the H and Q10 groups (455 +/- 61 and 487 +/- 57 x 10(3) microns 2) than in the P group (636 +/- 72 x 10(3) microns 2) (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate and pulse pressure amplification in hypertensive subjects

BACKGROUND Although mean blood pressure (MBP) remains unmodified along the arterial tree, pulse pressure (PP) increases physiologically from the central to the peripheral arteries. Amplification of PP is known to be influenced by heart rate (HR), but the impact of this alteration has never been tested in patients with hypertension. METHODS A total of 712 hypertensive subjects, either treated or untreated, were divided into three classes of HR level. Carotid and brachial systolic blood pressure (SBP), carotid augmentation index, a marker of wave reflections, and carotid-brachial PP amplification were measured using applanation tonometry. RESULTS Independent of age, sex, and antihypertensive drugs, subjects with HR >80 beats/min were characterized, in comparison with those with lower HR, by reduced carotid SBP, PP, and augmentation index, resulting in a significant increase in PP amplification. In men but not in women, this pattern was associated with higher values of brachial SBP and DBP and by higher incidences of elevated glycemia and atherosclerotic alterations. In the male population, PP amplifications was, independent of HR, associated with the presence of beta blocking agents (negative association) and elevated plasma glucose. CONCLUSIONS Hypertensive men and women with high HR have significant PP amplifications, principally because of reduced central SBP and disturbed wave reflections. beta-blocking agents and plasma glucose independently alter PP amplification in men but not in women. Whether these opposite patterns influence the gender difference in cardiovascular risk should be prospectively studied.

Association between 24-hour ambulatory heart rate and arterial stiffness.

Clinical and experimental studies point to a positive association between carotid-femoral pulse wave velocity (PWVcf) and casual heart rate. However, an association with 24-h ambulatory heart rate has never been investigated. Twenty-four hour ambulatory heart rate and PWVcf (automatic computerised technique) were simultaneously measured in 213 subjects with untreated mild-to-moderate essential hypertension. It was found that mean ambulatory heart rate was higher in women than in men but the difference reached statistical significance only in those below 50 years of age during night-time measurements. As well as age and blood pressure, 24-h ambulatory heart rate was also an independent factor influencing PWVcf. Independent of gender, the relationship between PWVcf and ambulatory heart rate was stronger in patients over 50 years of age. Casual heart rate was not a significant determinant of PWVcf in this population. In conclusion, ambulatory heart rate contribution to explain pulse wave velocity is more important than casual heart rate. The relationship between 24-h heart rate and pulse wave velocity is stronger for subjects older than 50 years of age independent of gender.

Carotid Artery Mechanical Properties of Dahl Salt-Sensitive Rats

We evaluated the mechanical properties of the carotid artery in anesthetized Dahl rats with or without long-term treatment with the diuretic compound indapamide. The mechanical properties of the carotid artery were evaluated by establishing pressure-volume curves in situ in vivo before and after total relaxation of arterial smooth muscle by potassium cyanide. Dahl salt-sensitive and salt-resistant rats were fed either a low (0.4%) or high (7%) NaCl diet for 5 weeks. In each group, half the rats received for the same period of time oral treatment with indapamide (3 mg/kg per day). Blood pressure, heart rate, and pressure-volume curves were studied at the end of the 5-week period. In untreated Dahl salt-sensitive rats, the pressure-volume curve of the carotid artery was shifted to the right compared with that in untreated Dahl salt-resistant rats. The finding was observed even after potassium cyanide and regardless of the NaCl diet (P < .01 between Dahl salt-sensitive and -resistant rats). Indapamide was able to prevent the development of hypertension in Dahl salt-sensitive rats receiving a high NaCl diet (185 +/- 7 versus 146 +/- 8 mm Hg in untreated and treated Dahl salt-sensitive rats with a high NaCl diet, P < .0005). In the other groups, indapamide had no effect on blood pressure. Indapamide treatment increased carotid arterial static compliance in Dahl salt-sensitive rats with a high or low NaCl diet and to a lesser extent in Dahl salt-resistant rats. The increase was observed even after total relaxation of carotid arterial smooth muscle by potassium cyanide.(ABSTRACT TRUNCATED AT 250 WORDS)

RESTING HEART RATE IN OLDER PEOPLE: A PREDICTOR OF SURVIVAL TO AGE 85

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Selective reduction of heart rate by ivabradine: effect on the visco-elastic arterial properties in rats.

Background The heart rate (HR) reduction obtained by ivabradine is associated in rats with a decrease in diastolic blood pressure (DBP) and mean blood pressure (MBP), and with an increased pulsatile carotid arterial diameter. Objective To determine, in spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) rats, whether acute reductions of the HR in response to ivabradine induced changes in the carotid visco-elastic behavior, as assessed by echo-tracking techniques. Methods The hysteresis of the carotid diameter/pressure curve was used to determine the dissipated energy per cardiac cycle, a classical index of arterial viscosity. Four doses of 1 mg/kg intravenous ivabradine were repeated in anesthetized rats to obtain subsequent HR reductions. Results In WKY, repeated administration of ivabradine produced reduction of MBP, DBP and HR, without change of systolic blood pressure (SBP). In SHR, ivabradine produced a higher reduction in DBP, SBP and HR than in WKY rats, but the increase in pulse pressure was similar in both strains. In SHR and WKY rats, ivabradine did not modify the incremental elastic modulus–stress curves, and shifted the distensibility–pressure curves through changes in blood pressure, indicating no modification in isobaric carotid stiffness. In both strains, ivabradine produced an identical increase of the energy dissipated per cardiac cycle. Conclusion In WKY rats and SHR, acute ivabradine reduces MBP and DBP and increases pulse pressure, but without change in arterial stiffness. In both strains, the HR reduction due to ivabradine induces an identical increase of the energy dissipation of the arterial wall.

Acute and long-term effects of angiotensin converting enzyme inhibition on larger arteries and cardiac hypertrophy: mechanical and structural parameters.

Aim of studies The extent of cardiovascular alterations in hypertension is related quantitatively to the degree of hypertension. However, there is increasing evidence that humoral processes, which are not dependent on blood pressure, are of major importance in these alterations. In particular, angiotensin converting enzyme (ACE) activity seems to be involved. We therefore compared the effects of blood pressure reduction and of acute and long-term ACE inhibition on cardiac hypertrophy, arterial function and morphologic alterations in hypertension. Acute study To examine the acute effect of ACE inhibition on arterial compliance, we used an experimental model allowing a pressure-volume determination in the carotid artery in situ to assess arterial compliance in normotensive Wistar-Kyoto and spontaneously hypertensive rats. The pressure-volume relationship was determined after an acute, single, oral administration of either placebo or the ACE inhibitor quinapril in doses of 0.3 and 3mg/kg. Both doses of quinapril produced a similar relaxation of arterial smooth muscle, approximately 80–90% of the maximum relaxation produced by potassium cyanide. Long-term study We then studied the long-term effects of ACE inhibition compared with those of hydralazine. Four groups of 4-week-old spontaneously hypertensive rats were treated for 4 months with quinapril at 1 or 10mg/kg per day, hydralazine at 15 mg/kg per day or placebo. Blood pressure, plasma and aortic ACE activity, left ventricular weight and histomorphometric parameters of the thoracic aorta, the renal and the mesenteric arteries were evaluated. We found a marked dissociation between the effects on blood pressure and cardiovascular structural parameters. Whereas both hydralazine and 10 mg/kg quinapril prevented the development of hypertension and aortic hypertrophy in a pressure-dependent manner, only the ACE inhibitor prevented left ventricular hypertrophy and aortic collagen accumulation. These quinapril effects were observed even with a small non-antihypertensive dose (1 mg/kg); the effect on aortic collagen was related to a reduction in aortic but not plasma ACE. Conclusions These results indicate that the acute and long-term effects of ACE inhibitors on arterial function and structure go well beyond their antihypertensive actions and seem to be related to inhibition of tissue ACE. However, while clear effects were observed in the particular arterial segment explored, it may not be valid to extrapolate these findings to other arterial segments.

Physiological and pharmacological changes in the carotid artery pressure-volume curve in situ in rats.

Aim To measure the mechanical properties of the rat carotid artery as affected by physiological and pharmacological changes. Methods We used an in situ measurement method that did not affect the anatomy, vascularization or innervation of the carotid artery, in normotensive and in spontaneously hypertensive rats (SHR), to evaluate the effects of ageing, hypertension and acute or chronic drug-induced vasorelaxation. Results The compliance-pressure curve was characterized, under baseline conditions, by two phases, an ascending component in the lower pressure ranges and a descending component in the higher pressure ranges. In younger or older normotensive rats the maximum value of carotid compliance was observed for values of transmural pressure that approximated those of the operating mean blood pressure. For any given value of transmural pressure, carotid compliance was lower in the hypertensive rats, whether younger (3 months) or older (18 months), than in normotensive rats. This finding was particularly striking for transmural pressures below 125 mmHg, and held true even after the administration of potassium cyanide. Consequently, the reduced compliance in the hypertensive rats was attributed predominantly to structural changes in the arterial wall. Moreover, in the hypertensive rats there was a dissociation between the operating arterial blood pressure level and the maximum value of carotid arterial compliance. Thus in young SHR, whereas the operating systemic blood pressure was shifted toward higher values (> 175 mmHg), the maximum value of carotid compliance was observed for pressure levels close to 125 mmHg. This dissociation was more pronounced in older SHR (mean blood pressure 200 mmHg; maximum compliance 75 mmHg). Conclusions The acute administration of vasodilators or of potassium cyanide induces relaxation of vascular smooth muscle and increases compliance for distension pressures of up to 125 mmHg. Since the drugs had no effects on arterial compliance at higher pressure levels, we conclude that in SHR acute vasorelaxation can increase operating compliance only if blood pressure is reduced. In contrast, chronic treatment with vasodilating agents is able to increase compliance even for higher blood pressure levels. Therefore, we suggest that chronic treatment can improve the elastic properties of the arterial wall through changes in the arterial wall structure.

Reduced variability and execution time to reach a target with a needle GPS system: Comparison between physicians, residents and nurse anaesthetists

Ultrasound (US) guided needle positioning is safer than anatomical landmark techniques for central venous access. Hand-eye coordination and execution time depend on the professionals ability, previous training and personal skills. Needle guidance positioning systems (GPS) may theoretically reduce execution time and facilitate needle positioning in specific targets, thus improving patient comfort and safety. Three groups of healthcare professionals (41 anaesthesiologists and intensivists, 41 residents in anaesthesiology and intensive care, 39 nurse anaesthetists) were included and required to perform 3 tasks (positioning the tip of a needle in three different targets in a silicon phantom) by using successively a conventional US-guided needle positioning and a needle GPS. We measured execution times to perform the tasks, hand-eye coordination and the number of repositioning occurrences or errors in handling the needle or the probe. Without the GPS system, we observed a significant inter-individual difference for execution time (P<0.05), hand-eye coordination and the number of errors/needle repositioning between physicians, residents and nurse anaesthetists. US training and video gaming were found to be independent factors associated with a shorter execution time. Use of GPS attenuated the inter-individual and group variability. We observed a reduced execution time and improved hand-eye coordination in all groups as compared to US without GPS. Neither US training, video gaming nor demographic personal or professional factors were found to be significantly associated with reduced execution time when GPS was used. US associated with GPS systems may improve safety and decrease execution time by reducing inter-individual variability between professionals for needle-handling procedures.