Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes.

BACKGROUND: Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. METHODS: Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1µM), propofol (1µM), or propofol plus doxorubicin (given 1h post propofol). After 24h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. RESULTS: Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-δ was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. CONCLUSIONS: Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.

A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor.

Because angiotensin-converting enzyme (ACE) activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage genome-wide association study: (1) from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects. In the first stage, eight single nucleotide polymorphisms (SNPs) of the ACE structural gene and one SNP of ABO genes were significantly associated with ACE activity. SNP rs4343 in exon17 near the well-known insertion/deletion polymorphism had the strongest association. We confirmed in the second stage that three SNPs: rs4343 in ACE gene (P=3.0 x 10⁻²5), rs495828 (P=3.5 x 10⁻8) and rs8176746 (P=9.3 x 10⁻5) in ABO gene were significantly associated with ACE activity. We further replicated the association between ABO genotype/blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees), and showed a potential differential blood pressure response to ACEI in subjects with varied numbers of ACE-activity-raising alleles. These findings may broaden our understanding of the mechanisms controlling ACE activity and advance our pharmacogenetic knowledge on ACEI.

Impact of chronic advanced aortic regurgitation on the perioperative outcome of noncardiac surgery.

BACKGROUND: Whether and how chronic advanced aortic regurgitation (AR) impacts the perioperative outcome of noncardiac surgery remains unclear. METHODS: From November 1999 to December 2006, all patients undergoing noncardiac operations and ever examined by echocardiography within the last 6 months were screened. Those with chronic moderate-severe or severe AR were enrolled, provided they were not already trachea-intubated or aortic valve operated, and the surgery was not performed under local anesthesia. Case-matched subjects without significant AR served as controls. The perioperative outcomes of these patients were analyzed, and independent prognostic correlates were investigated by multivariate logistic regression analysis. RESULTS: A total of 167 patients (male 131, mean age of 75 years) complying with the enrollment criteria were studied. Compared with the other 167 case-matched control peers, patients with advanced AR risked potential hazards of serious hemodynamic instability (0.6%) and circulatory collapse (1.2%) during surgery despite the similar incidence of overall cardiac adverse events, and were further distressed with more cardiopulmonary complications (16.2% vs. 5.4%, P=0.003) and in-hospital deaths (9% vs. 1.8%, P=0.008) post-operatively. Multivariate regression analysis confirmed the correlation of advanced AR with perioperative mortality, and identified depressed left ventricular function, renal dysfunction, high surgical risk, and lack of cardiac medication as predictors of in-hospital death. CONCLUSION: Chronic advanced AR complicates the perioperative outcome of noncardiac surgery as reflected by frequent cardiopulmonary morbidities and in-hospital deaths, especially when coexisting with specified high-risk clinical and surgical characteristics.

A rapidly evolving homeobox at the site of a hybrid sterility gene.

The homeodomain is a DNA binding motif that is usually conserved among diverse taxa. Rapidly evolving homeodomains are thus of interest because their divergence may be associated with speciation. The exact site of the Odysseus (Ods) locus of hybrid male sterility in Drosophila contains such a homeobox gene. In the past half million years, this homeodomain has experienced more amino acid substitutions than it did in the preceding 700 million years; during this period, it has also evolved faster than other parts of the protein or even the introns. Such rapid sequence divergence is driven by positive selection and may contribute to reproductive isolation.

Caffeic acid phenethyl ester inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using a local delivery system.

Over the last two decades, significant advances have been made in percutaneous coronary intervention (PCI) for the treatment of atherosclerotic plaques. However, restenosis after PCI still challenges both vascular biologists and interventional cardiologists. In this study, we found that caffeic acid phenethyl ester (CAPE) displayed an inhibitory effect on human coronary smooth muscle cell (HCSMC) growth and migration. Flow cytometry analysis showed that the ratio of S phase increased after exposing cells to CAPE for 48-72 h. Pretreatment of cells with CAPE significantly suppressed Cyclin E, CDK2, Cyclin A, and proliferating-cell nuclear antibody expression. We demonstrated that CAPE inhibited AKT 1 and MEK1/2 activation. Using a local infusion system, CAPE was able to regress the intima thickening of the iliac artery in rabbits after balloon injury. The percentage of intimal thickening decreased significantly to 55.0 +/- 0.12 in the group after local CAPE infusion compared to the group after saline infusion (98.3 +/- 0.41%). In conclusion, CAPE can inhibit the proliferation and migration of HCSMCs by inducing cell cycle arrest. Decreased cell cycle genes and associated signaling pathway target gene expression may mediate anti-proliferative and anti-migration effects of CAPE. Furthermore, CAPE prevents intima thickening in rabbits after balloon angioplasty. These results indicate that CAPE may have therapeutic relevance for the prevention of restenosis during PCI in the treatment of coronary artery diseases.

Arterial hemodynamics in human hypertension.

Differences in aortic impedance between normotensives and hypertensives are not well characterized. We examined impedance in 8 normotensive and 11 hypertensive (mean 96.7 vs. 122.2 mmHg) age-matched, Chinese patients undergoing cardiac catheterization at rest, during nitroprusside, and handgrip exercise before and after beta blockade (propranolol). Hypertensives had higher resistance (2,295 vs. 1713 dyn-s/cm5), characteristic impedance (145.7 vs. 93.9 dyn-s/cm5), total external power (1,579 vs. 1174 mW), peripheral reflections (ratio of backward to forward wave components of 0.54 vs. 0.44), and first zero crossing of impedance phase angle (4.15 vs. 2.97 Hz). These abnormalities were eliminated with vasodilatation. Differences between groups were not further exacerbated when pressure was increased during handgrip exercise. Beta blockade further increased resistance and reflections. Thus, hemodynamic abnormalities of essential hypertension (increased resistance, reflections, and pulse wave velocity, and decreased compliance) are compatible with an increased vasomotor tone that is further unmasked during generalized beta blockade.

Pulmonary veins and ligament of Marshall as sources of rapid activations in a canine model of sustained atrial fibrillation.

BACKGROUND: In dogs, chronic rapid pacing may result in sustained atrial fibrillation (AF). However, activation patterns in pacing-induced sustained AF are unclear. METHODS AND RESULTS: We induced sustained AF (>48 hours) in 6 dogs by rapid pacing for 139+/-84 days. We then performed computerized atrial epicardial mappings and recorded the activations in the ligament of Marshall (LOM) and the pulmonary veins (PVs). During AF, mean activation cycle length in the right atrial free wall (126+/-17 ms) was significantly longer than that in the left atrial free wall (96+/-5 ms, P:=0.006). In addition, mean activation cycle length in the left atrial free wall was significantly longer than that in the LOM (84+/-5 ms, P:<0.001), the left inferior PV (81+/-4 ms, P:=0.001), and the left superior PV (85+/-7 ms, P:=0.003). Similarly, the dominant frequency was highest in the LOM and the PVs (range 11.2 to 13.3 Hz), followed by the left and right atria (P:<0.001). In all dogs studied, rapid and complicated electrograms were consistently observed at the LOM and the PVs. During AF, both wandering wavelets and organized reentry were present. There were more wave fronts in the left atrium than in the right atrium (P:<0.001). CONCLUSIONS: In chronic pacing-induced sustained AF, the LOM and the PVs are the sources of rapid activations. The mechanism by which the left atrium activates faster and has more wave fronts than the right atrium may relate to the fact that the left atrium is closer to the sources of rapid activations.

Progressive action potential duration shortening and the conversion from atrial flutter to atrial fibrillation in the isolated canine right atrium.

OBJECTIVES: We sought to evaluate the effects of progressive shortening of the action potential duration (APD) on atrial wave front stability. BACKGROUND: The mechanisms of conversion from atrial flutter to atrial fibrillation (AF) are unclear. METHODS: Isolated canine right atria were perfused with 1 to 5 micromol/l of acetylcholine (ACh). We mapped the endocardium by using 477 bipolar electrodes and simultaneously recorded transmembrane potentials from the epicardium. The APD(90) was measured during regular pacing (S(1)) with cycle lengths of 300 ms. Atrial arrhythmia was induced by a premature stimulus (S(2)). RESULTS: At baseline, only short runs of repetitive beats (<10 cycles) were induced. After shortening the APD(90) from 124 +/- 15 ms to 72 +/- 9 ms (p < 0.01) with 1 to 2.5 micromol/l of ACh, S(2) pacing induced single, stable and stationary re-entrant wave fronts (307 +/- 277 cycles). They either anchored to pectinate muscles (5 tissues) or used pectinate muscles as part of the re-entry (4 tissues). When ACh was raised to 2.5 to 5 micromol/l, the APD(90) was further shortened to 40 +/- 12 ms (p < 0.01); S(2) pacing induced in vitro AF by two different mechanisms. In most episodes (n = 13), AF was characterized by rapid, nonstationary re-entry and multiple wave breaks. In three episodes with APD(90) <30 ms, AF was characterized by rapid, multiple, asynchronous, but stationary wave fronts. CONCLUSIONS: Progressive APD shortening modulates atrial wave front stability and converts atrial flutter to AF by two mechanisms: 1) detachment of stationary re-entry from the pectinate muscle and the generation of multiple wave breaks; and 2) formation of multiple, isolated, stationary wave fronts with different activation cycle lengths.

Incipient speciation by sexual isolation in Drosophila melanogaster: extensive genetic divergence without reinforcement.

The collection of Drosophila melanogaster from Zimbabwe and nearby regions (the Z-type) yield females who would not mate with the cosmopolitan D. melanogaster males (the M-type). To dissect the genetic basis of this sexual isolation, we constructed 16 whole-chromosome substitution lines between two standard Z- and M-lines. The results were as follows: (1) All substitution lines appear normal in viability and fertility in both sexes, indicating no strong postmating isolation. (2) The genes for the behaviors are mapped to all three major chromosomes with the same ranking and comparable magnitude of effects for both sexes: III > II >> X > or = 0 (III, II and X designate the effects of the three chromosomes). The results suggest less evolution on the X than on autosomes at loci of sexual behavior. (3) The genes for "Z-maleness" are many and somewhat redundant. Whole-chromosome effects for Z-maleness appear nearly additive and show little dominance. (4) In contrast, "Z-femaleness" has less redundancy as partial genotypes never exhibit full phenotypic effects. Epistatic interactions and incomplete dominance can sometimes be detected. (5) The extensive genetic divergence underlying sexual isolation has evolved in the absence of detectable reduction in hybrid fitnesses. Sexual selection has apparently been a driving force of multiple facets of speciation at the nascent stage without reinforcement.

Differential glucose tolerance in dipper and nondipper essential hypertension: the implications of circadian blood pressure regulation on glucose tolerance in hypertension.

OBJECTIVE: The goals of this study were to compare glucose tolerance in dipper and nondipper hypertensive patients and to explore the cause of glucose intolerance in essential hypertension. RESEARCH DESIGN AND METHODS: A total of 50 patients <45 years old who had essential hypertension were recruited and studied by 24-h blood pressure monitoring and an oral glucose tolerance test (OGTT). Autonomic function was assessed with spectral analysis of heart rate variability RESULTS: Dipper hypertensive patients (n=25) had lower nocturnal blood pressure than nondipper (n=25) patients. During OGTT, postprandial glucose levels were higher in the nondippers at 0, 90, and 120 min (all P < 0.05). Nondippers had a higher fasting insulin/glucose ratio than was apparent in normal control subjects. Despite higher postprandial glucose levels, nondippers had lower postprandial insulin levels. These results suggest that nondippers were insulin resistant and that their pancreatic beta-cell function was impaired. For all patients, nocturnal reduction of blood pressure was inversely related to total glucose levels under the OGTT curve and was positively related to postprandial insulin levels. Daytime heart rate did not differ between the dippers and nondippers, but nocturnal heart rate was higher in the nondippers, suggesting that nocturnal sympathetic activities were higher among the nondippers. Spectral analysis of heart rate variability suggests that the nondippers had lower parasympathetic activities and unbalanced sympathetic/parasympathetic outflow. CONCLUSIONS: These findings indicate that nondipper hypertensive patients are more glucose intolerant than are dipper patients. The abnormalities of glucose metabolism in nondippers could be explained by insulin resistance and beta-cell dysfunction. The results of spectral analysis suggest that abnormal autonomic outflow may represent a possible link between hypertension and associated metabolic dysfunction.

Regional pulse wave velocities in hypertensive and normotensive humans.

STUDY OBJECTIVE: The aim was to compare regional wave transmission and reflection properties along the aorta in age matched normotensive and hypertensive subjects. DESIGN: Simultaneous upstream and downstream micromanometer pressures were recorded at five regions from the ascending aorta to the iliac artery. Recordings were made in the baseline condition in both groups and during sustained isometric handgrip exercise in the normotensives to see if increasing the blood pressure to hypertensive levels would eliminate baseline differences between the two groups. SUBJECTS: Only subjects who had no coronary or valvular heart disease were studied. Normotensive subjects (n = 8) were selected from those undergoing electrophysiological testing whose blood pressures were consistently in the normal range (systolic less than 140, diastolic less than 90 mm Hg). Age matched hypertensive subjects (n = 17) were those in whom secondary causes of hypertension were excluded and who had repeated measurements of raised blood pressure. MEASUREMENTS AND RESULTS: In each region pulse wave velocity was estimated from the simultaneous upstream and downstream pressure records using the foot to foot method, and apparent phase velocity was obtained from Fourier analysis of the two pressures. The intensity of wave reflections was judged by the magnitude of fluctuations of the harmonics of apparent phase velocity about the mean of the higher frequency harmonics. In both groups in the baseline state there were regional variations in the pulse wave velocity with the lowest values occurring just proximal to the renal arteries and highest values occurring in the iliac artery. Likewise, in both groups the extent of wave reflections varied regionally--pronounced reflections were seen in the ascending aorta and from just proximal to the renal arteries to the aortic bifurcation but not in the mid-thoracic or iliac regions. The hypertensives had higher pulse wave velocity than normotensives only in the iliac artery (780 v 567 cm.s-1) and had more reflections in the three regions in which reflections were evident. Although handgrip in the normotensive group eliminated regional differences in pulse wave velocity between the groups, reflections were still greater in the hypertensives. CONCLUSIONS: Essential hypertension affects the regional properties of the aortic wall. These alterations are manifested by increased peripheral wave-speed and increased wave reflections along the aorta. The differences in wavespeed but not reflection properties are eliminated when the pressures are matched by handgrip, suggesting that factors other than the level of blood pressure per se are responsible for the alterations in reflection properties.

Insulin-like growth factor I improves cardiovascular function and suppresses apoptosis of cardiomyocytes in dilated cardiomyopathy.

To investigate how insulin-like growth factor I (IGF-I) modulates cardiovascular function and myocardial apoptosis in heart failure, the therapeutic effects of IGF-I were determined in a canine model of dilated cardiomyopathy. The animals were paced at 220 beats/min, and the left ventricular (LV) chamber became dilated after 2 weeks. A subset of paced dogs was treated with s.c. injections of IGF-I from week 3 to week 4. After 4 weeks of pacing, untreated paced dogs developed significant ventricular dysfunction. IGF-I-treated paced dogs showed better cardiac output, stroke volume, LV end-systolic pressure, and LV end-diastolic pressure. Moreover, pulmonary wedge pressure and systemic vascular resistance were increased in the untreated group and decreased in the IGF-I-treated group. IGF-I treatment was associated with less thinning of the ventricular wall. Compared with the controls, untreated paced dogs showed increased apoptosis of cardiac muscle cells, which was partially suppressed by IGF-I treatment. The myocardial apoptotic index was negatively related to the thickness of the ventricular wall and to cardiac output, suggesting that ventricular remodeling/dysfunction involves the occurrence of myocardial apoptosis. Due to the close resemblance between this experimental model of dilated cardiomyopathy and human heart failure, the results of this study provide evidence that IGF-I may be a potential therapeutic agent for the failing human heart.

Arterial hemodynamics in human hypertension. Effects of the calcium channel antagonist nifedipine.

Previous studies have shown some distinct hemodynamic alterations in essential hypertension, including increased resistance, wave reflections, and pulse wave velocity and decreased arterial compliance. These abnormalities are completely normalized by nonspecific smooth muscle dilation with nitroprusside but not by combined alpha- and beta-adrenergic blockade or angiotensin-converting enzyme inhibition, suggesting an enhanced smooth muscle tone that cannot be attributed solely to the sympathetic nervous or renin-angiotensin systems. Since hypertensive patients have an enhanced calcium influx-dependent vasoconstriction, we performed the present study to examine the extent to which the dihydropyridine calcium channel antagonist nifedipine could normalize the hemodynamic abnormalities in essential hypertension. An essential hypertensive patient group was compared with a normotensive group similar in age, body size, and proportion of men and women. During diagnostic cardiac catheterization, ascending aortic micromanometer pressures and electromagnetic flows were measured at baseline and after sufficient sublingual nifedipine (mean, 24 mg) to normalize blood pressure. From the pressures and flows, aortic input impedance, wave reflection magnitude, and compliance were computed. In the hypertensive group, the hemodynamic alterations were indistinguishable from those summarized above. Nifedipine produced sufficient vasodilation to completely normalize all of these hemodynamic alterations, including wave reflections. From these results, together with those reported in our previous studies, it is clear that the various classes of antihypertensive agents affect hemodynamics differently. All are capable of decreasing blood pressure to normotensive levels, but only nitroprusside and nifedipine can also completely normalize all the other pulsatile hemodynamic alterations. Thus, these hemodynamic effects of the different classes of antihypertensive agents should be considered in choosing a therapeutic modality.

Arterial hemodynamics in human hypertension. Effects of angiotensin converting enzyme inhibition.

Previous studies have shown some distinct hemodynamic alterations in essential hypertension, including increased resistance, wave reflections, and pulse wave velocity and decreased systemic compliance. These abnormalities are completely normalized by nonspecific smooth muscle dilation with nitroprusside but not by combined alpha- and beta-adrenergic blockade. The renin-angiotensin system, acting possibly via both circulating and local tissue effects, is thought to play an important role in essential hypertension, so its role in the altered hemodynamics deserves careful investigation. A hypertensive patient group was compared with a normotensive group similar in age, body size, and proportion of men and women. During diagnostic cardiac catheterization, ascending aortic micromanometer pressures and electromagnetic flows were measured in the baseline state. Intravenous captopril of a sufficient dosage (11 mg) to normalize blood pressure then was given to the hypertensive patients while measurements were repeated. From the pressures and flows, aortic input impedance, wave reflection magnitude, and compliance were computed. In the hypertensive group, the important hemodynamic alterations consisted of increased peripheral resistance, first zero crossing of aortic impedance phase angle, and wave reflections and decreased systemic compliance. Captopril had a pronounced hemodynamic effect. It normalized blood pressure, resistance, and impedance phase angle zero crossing. Compliance, although increased substantially by captopril, was still slightly lower than normotensive levels. The magnitude of wave reflections, although substantially lowered by angiotensin converting enzyme inhibition, was still persistently greater than normal. The present results, together with those previously reported, demonstrate that a complex interplay of factors underlies the increased smooth muscle tone in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Short- and long-term effects of antihypertensive drugs on arterial reflections, compliance, and impedance.

This article reviews our work on the effects of different classes of antihypertensive agents on the hemodynamic alterations in essential human hypertension. Short-term studies were done during cardiac catheterization in young normotensive subjects (mean age, 33 years; range, 19 to 40) and several different age-matched (range, 25 to 53 years) groups of patients with essential hypertension. Aortic impedance, resistance, wave reflections, and compliance were calculated from high-fidelity recordings of ascending aortic pressure and flow signals during baseline and after nitroprusside, propranolol followed by phentolamine, phentolamine, captopril, and nifedipine, respectively, at doses sufficient to normalize blood pressure in each hypertensive group. Propranolol exacerbated all the hemodynamic parameters; these effects were only partially overcome by phentolamine. Among the other agents only phentolamine did not completely normalize compliance, and only captopril did not completely normalize wave reflections. The long-term study was a randomized, double-blind comparison of fosinopril and atenolol in 79 normotensive subjects and 79 essential hypertensive patients. Baseline 24-hour ambulatory blood pressures and carotid artery tonometry to index wave reflections were performed in all subjects and in hypertensive patients after 8 weeks of therapy. Both fosinopril and atenolol normalized blood pressure and lowered the elevated augmentation index, but fosinopril had a significantly larger effect than atenolol. Both short- and long-term beta-blockade did not have as beneficial an effect as the other agents. Thus, the differing hemodynamic effects of the various classes of antihypertensive agents might be a consideration in the choice of therapy.

Changes of the insulin-like growth factor I system during acute myocardial infarction: implications on left ventricular remodeling.

In vitro and in vivo experiments have shown important biological actions of insulin-like growth factor I (IGF-I) in heart. The aims of this study were to determine the changes in circulating IGF-I and IGF-binding proteins (IGFBPs) during acute myocardial infarction (AMI) and to explore the relationship between IGF-I levels and myocardial remodeling and function after AMI. Thirty-four patients with acute Q-wave AMI and 17 matched controls were investigated in this study. Compared to normal subjects, free IGF-I and IGFBP-3 were significantly elevated, and IGFBP-1 was decreased upon AMI. Myocardial remodeling occurred after AMI in these patients. The day 2, 3, and 7 total IGF-I levels were inversely related to day 7 left ventricular (LV) end-diastolic, end-systolic diameters (r = -0.395 to -0.516) and LV mass (r = -0.487 to -0.661). Moreover, total IGF-I levels were positively related to LV ejection fraction (r = 0.402-0.453). Compared to the healthy survivors, those patients with poor outcomes had lower total IGF-I levels immediately after AMI. Most healthy survivors had total IGF-I levels greater than 137 ng/mL, but all patients with poor outcome had total IGF-I levels less than 137 ng/mL. Thus, AMI is associated with significant alterations in the IGF-I system. A higher total IGF-I level immediately after the onset of AMI is associated with better myocardial remodeling and ventricular function.

Aortic compliance in human hypertension.

Aortic compliance in normotensive and hypertensive Chinese subjects undergoing diagnostic cardiac catheterization was compared by using a newly described method that allows for determination of the pressure dependence of compliance if one assumes a value for the exponential coefficient of the pressure-volume relation of the large arteries. Under baseline conditions in the normotensive and hypertensive groups at mean aortic pressures of 96.3 and 128.6 mm Hg, aortic compliance averaged 1.47 and 0.80 ml/mm Hg, respectively. Compliance in the hypertensive group at a diastolic pressure of 99.4 mm Hg (which was nearly equal to the mean normotensive pressure) was 1.072 ml/mm Hg--still significantly lower than in the normotensive group. During nitroprusside infusion, however, the compliances in the hypertensive group increased to levels equal to or greater those in the normotensive group. Thus, these data confirm that aortic compliance is lower in hypertensive than in normotensive humans. They further demonstrate that the lower compliance cannot be attributed entirely to the elevated blood pressure, suggesting that excess smooth muscle tone may be partly responsible.

Validation of carotid artery tonometry as a means of estimating augmentation index of ascending aortic pressure.

Our objective was to validate a carotid artery tonometry-derived augmentation index as a means to estimate augmentation index (AI) of ascending aortic pressure under various physiological conditions. A total of 66 patients (50 men, 16 women; mean age, 55 years; range, 21 to 78 years; 44 in Taiwan and 22 in the United States) undergoing diagnostic catheterization were studied. Arterial pressure contours were obtained simultaneously from the right common carotid artery by applanation tonometry with an external micromanometer-tipped probe and from the ascending aorta by a micromanometer-tipped catheter at baseline (n = 62), after handgrip (n = 36), or after sublingual nitroglycerin administration (n = 17). The AI (expressed as percentage values) was calculated as the ratio of amplitude of the pressure wave above its systolic shoulder to the total pulse pressure. The carotid AI was consistently lower than the aortic AI, but the two were highly correlated at baseline and after both handgrip and nitroglycerin. Mean +/- SD and correlation coefficients were baseline (14 +/- 16, 28(+) +/- 17, .77), handgrip (18 +/- 19, 32(+) +/- 15, .86), and nitroglycerin (7 +/- 12, 18(+) +/- 13, .52). In addition, after adjusting for age, sex, height, blood pressure, heart rate, and study site, the changes of both AIs from baseline values with handgrip or nitroglycerin were highly associated such that the aortic AI could be approximated from the carotid AI with appropriate regression equations. The high correlations and predictable changes after interventions between the central AI and those estimated from noninvasive carotid tonometry suggest that this technique may have wide applicability for many cardiovascular studies.

Validation of a method for noninvasive measurement of central arterial pressure.

The goal of this study was to validate a newly improved noninvasive method for calibrated measurement of the ascending portion of the central arterial pressure wave in humans. Noninvasive pressure waveforms were generated by measuring the time delay between the R wave of the electrocardiogram and onset of brachial artery flow (by Doppler) during computer-controlled upper arm cuff deflation. This delay shortens with falling cuff pressure (becoming near constant at and below diastolic pressure), so that a plot of pressure versus time delay yields the ascending portion of the arterial waveform. These waveforms were compared with simultaneous invasive ascending aortic pressures in 57 adult patients (31 by fluid manometer [group A] and 26 by catheter-tipped micromanometer [group B]) during routine cardiac catheterization. Patient age ranged from 26 to 77 years. Eighty percent of group A patients and 40% of group B had coronary artery disease. Noninvasive systolic and diastolic pressures were very similar to invasive values in both groups (Pni = 0.98 x Pi, r = 0.99, p < 0.0001). Instantaneous pressure differences between waveforms were also similar in both groups, averaging between 4.5 and 5.5 mm Hg. Micromanometer and noninvasive pressure data were also obtained before and after intravenous nitroglycerin (n = 5) and isometric handgrip (n = 8) and demonstrated good agreement. A potential application of these pressures is for estimating maximal ventricular power to assess systolic function. This was tested using invasive pressure-volume data from four patients under a variety of conditions (exercise, pacing, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)

Different effects of fosinopril and atenolol on wave reflections in hypertensive patients.

We conducted this study to compare the effects of fosinopril versus atenolol on peripheral blood pressure, central arterial wave reflection, and left ventricular mass in a group of patients with essential hypertension. We conducted a double-blind, randomized trial of fosinopril and atenolol in 79 hypertensive patients (52 men, 27 women; mean age, 45.8 +/- 8.5 years; range, 30 to 68 years). Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe. The extent of wave reflection was estimated by the augmentation index defined as the ratio of the amplitude of pressure wave above its systolic shoulder to the pulse pressure. The augmentation index, left ventricular mass index by two-dimensional echocardiography, and 24-hour ambulatory blood pressures were determined before and after 8 weeks of daily treatment with fosinopril (10 to 20 mg) or atenolol (50 to 100 mg) with or without diuretics and compared with those values in 79 normotensive control subjects. After 8 weeks of treatment, both drugs lowered 24-hour ambulatory peripheral systolic and diastolic pressures into the normal range to a similar extent (fosinopril, -18/-13 mm Hg; atenolol, -23/-17 mm Hg, both P = NS). On the other hand, whereas the elevated augmentation index in hypertensive patients compared with normotensive subjects (16 +/- 11% versus 10 +/- 8%) was completely normalized by fosinopril (-9.3 +/- 9.8%, P < or = .002), it was lowered by atenolol (-4.8 +/- 8.9%, P < .002) but to a significantly smaller extent (fosinopril versus atenolol effect, P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)