A. H. Van Den Meiracker

Reconstruction of Brachial Artery Pressure From Noninvasive Finger Pressure Measurements

BACKGROUND Pulse wave distortions, mainly caused by reflections, and pressure gradients, caused by flow in the resistive vascular tree, may cause differences between finger and brachial artery pressures. These differences may limit the use of finger pressure measurements. We investigated whether brachial artery pressure waves could be reconstructed from finger pressure measurements by correcting for the pressure gradient in addition to correction for pulse wave distortion with a previously described filter. METHODS AND RESULTS Finger artery pressure (with Finapres), intra-arterial brachial artery pressure (BAP), Riva-Rocci/ Korotkoff (RRK), oscillometric, and return-to-flow (RTF) measurements were simultaneously performed in 57 healthy elderly subjects and patients with vascular disease and/or hypertension. A generalized waveform filter was used to correct for pulse wave distortions. Correction equations for the pressure gradient, based on finger pressure, RRK, RTF, or oscillometric measurements, were obtained in 28 randomly selected subjects and tested in 29. Before reconstruction, Finapres underestimated mean and diastolic BAP (finger pressure minus BAP: systolic, -3.2 +/- 16.9 mm Hg; mean, -13.0 +/- 10.5 mm Hg; diastolic, -8.4 +/- 9.0 mm Hg [mean +/- SD]). After filtering, reconstructed BAP waves were similar to actual BAP in shape but not in pressure level. Optimal correction for the pressure gradient with an equation based on RTF measurements reduced the pressure differences to meet American Association for the Advancement of Medical Instrumentation criteria (reconstructed finger pressure minus BAP: systolic, 3.7 +/- 7.0 mm Hg; mean, 0.7 +/- 4.6 mm Hg; and diastolic, 1.0 +/- 4.9 mm Hg). CONCLUSIONS BAP waves can be reconstructed from noninvasive finger pressure registrations when finger pressure waves are corrected for pulse wave distortion and individual pressure gradients.

Circulating semicarbazide-sensitive amine oxidase is raised both in Type I (insulin-dependent), in Type II (non-insulin-dependent) diabetes mellitus and even in childhood Type I diabetes at first clinical diagnosis

Summary Plasma semicarbazide-sensitive amine oxidase is raised in patients with Type I (insulin-dependent) diabetes mellitus. It has been suggested that this enzyme is involved in the development of microvascular damage through its ability to convert amines (e. g. methylamine and aminoacetone) into aldehydes, hydrogen peroxide and ammonia. Plasma semicarbazide-sensitive amine oxidase was found to be equally raised both in patients with Type I diabetes (n = 73) and Type II (non-insulin-dependent) diabetes mellitus (n = 88) compared with control subjects (621 ± 209 and 619 ± 202 vs 352 ± 102 mU/l, p < 0.0001) and to correlate in multiple regression analysis with HbA1 c. Since the enzyme could protect the islets from the inhibitory effects of methylamine on insulin secretion, we also tested sera of 100 children, collected consecutively at first diagnosis of Type I diabetes, for semicarbazide-sensitive amine oxidase. The activity was greatly increased compared with serum values of 76 control (siblings) children (757 ± 300 vs 455 ± 138 mU/l, p < 0.0001), but not associated with HbA1 c. Our study confirms the increase of plasma semicarbazide-sensitive amine oxidase in Type I diabetes and extends this finding to Type II diabetes as well as to childhood Type I at first clinical diagnosis. In the last case increased enzyme activities could serve to protect the islets from inhibitory effects of methylamine but cause damage by generation of hydrogen peroxide, aldehydes and ammonia. In the long run the increased enzyme activities could also contribute to vascular damage by direct cytotoxic action on endothelial cells, including increased oxidative stress and glycosylation of proteins. [Diabetologia (1999) 42: 233–237]

Risk Factors for Hemodynamic Instability during Surgery for Pheochromocytoma

BACKGROUND Surgery on pheochromocytoma carries a risk for hemodynamic (HD) instability. The aim of this study was to identify preoperative risk factors for intraoperative HD instability. In addition, efficacy of pretreatment with the alpha-adrenergic receptor (alpha) antagonists phenoxybenzamine (PXB) and doxazosin (DOX) was compared with respect to reduction of intraoperative HD instability. METHODS Seventy-three patients operated in Erasmus Medical Center between 1995 and 2007 were included. Parameters studied were catecholamine type and concentration, tumor diameter, mean arterial pressure (MAP) before and after (MAP(alpha)) pretreatment with alpha-antagonist, postural fall in blood pressure (BP) after pretreatment, type of alpha-blockade, type of operation, and presence of a familial polytumor syndrome. HD instability was assessed by measuring the number and time period MAP was below 60 mm Hg and systolic BP (SBP) was above 160 mm Hg. RESULTS A correlation was found between the intraoperative time periods of SBP above 160 mm Hg and plasma norepinephrine levels (r = 0.23; P < 0.05), tumor diameter (r = 0.36; P < 0.01), and postural BP fall (r = 0.30; P < 0.05). MAP at presentation and after alpha-blockade above 100 mm Hg (BP, 130/85 mm Hg) was related to more and longer episodes with a SBP above 160 mm Hg (P < 0.01). Type of operation or alpha-blockade and presence of a familial polytumor syndrome were not related to intraoperative HD instability. Postoperative MAP was lower in the DOX group than in the PXB group (P < 0.05). CONCLUSION Risk factors for HD instability during surgery for pheochromocytoma include a high plasma NE concentration, larger tumor size, more profound postural BP fall after alpha-blockade, and a MAP above 100 mm Hg (130/85 mm Hg). Efficacy for preventing HD instability was identical for PXB and DOX.

Cardiovascular variability in major depressive disorder and effects of imipramine or mirtazapine (Org 3770).

Spectral analysis of fluctuations in heart rate (HR) and blood pressure (BP) was applied to assess sympathetic and parasympathetic cardiovascular control mechanisms in patients with unipolar affective disorder before and after treatment with imipramine (IMI) or mirtazapine (MIR). In a double-blind randomized study, 10 patients received treatment with IMI and 10 patients received treatment with MIR. Cardiovascular parameters were studied before and after 4 weeks of treatment: HR and BP (Finapres) were recorded continuously during supine rest (SR) and orthostatic challenge (OC; 60-degrees head-up tilting). During SR and OC, power spectra were calculated for HR and systolic BP. Spectral density was assessed for three frequency bands: low (0.02-0.06 Hz), mid (0.07-0.14 Hz), and high (0.15-0.50 Hz). Before treatment, the depressed patients (N = 20) differed from age-matched controls (N = 20) only in their response to OC: the depressed patients showed more suppression of HR variability (both mid- and high-frequency band fluctuations), indicating stronger vagal inhibition, and a reduced increase of BP variability (mid-frequency band fluctuations), indicating reduced sympathetic activation. After 4 weeks of treatment, patients treated with either antidepressant drug showed significant changes of HR (increase) and HR variability (decrease) during SR and OC; the suppression of mid- and high-frequency fluctuations of HR was larger for IMI than for MIR. The increase in HR and decrease in HR variability may be attributed to the anticholinergic properties of IMI (strong) and MIR (weak), resulting in cardiac vagal inhibition. Whereas MIR had no effect on BP or BP variability, IMI specifically reduced mid-frequency band fluctuations of BP as the result of a suppression of central sympathetic activity. Our data confirm and extend previous observations on the presence of autonomic dysfunctions in unmedicated depressed patients: spectral analysis of HR and BP fluctuations suggested that both parasympathetic and sympathetic mechanisms are involved, specifically during OC. The preexisting autonomic cardiovascular dysfunctions were not normalized by antidepressant drugs. In fact, some of the components of the cardiovascular autonomic dysfunction were further aggravated, depending on the pharmacologic profile of the drug under investigation.

Comparison of Finapres non-invasive beat-to-beat finger blood pressure with intrabrachial artery pressure during and after bicycle ergometry.

To evaluate the accuracy of continuous non-invasive blood pressure measurements in the finger during exercise, Finapres blood pressures of six normotensive healthy males were measured during increasing levels of bicycle exercise, using simultaneously registered ipsilateral intrabrachial artery pressures as a reference. At rest, finger systolic blood pressure was higher and finger diastolic and mean arterial pressures were lower than the corresponding intrabrachial pressures in five of the six subjects. During exercise, average finger diastolic and mean arterial pressures did not differ further from these intrabrachial pressures, but finger systolic pressure increased considerably more than the direct systolic pressure, exceeding it by 26 +/- 20 mmHg (mean +/- s.d.) at maximal exercise. This latter finding potentially limits the use of finger blood pressure measurements during exercise.

Prolonged blood pressure reduction by orally active renin inhibitor RO 42-5892 in essential hypertension.

OBJECTIVE--To investigate the effects of a novel specific renin inhibitor, RO 42-5892, with high affinity for human renin (Ki = 0.5 x 10(-9) mol/l), on plasma renin activity and angiotensin II concentration and on 24 hour ambulatory blood pressure in essential hypertension. DESIGN--Exploratory study in which active treatment was preceded by placebo. SETTING--Inpatient unit of teaching hospital. PATIENTS--Nine men with uncomplicated essential hypertension who had a normal sodium intake. INTERVENTIONS--Two single intravenous doses of RO 42-5892 (100 and 1,000 micrograms/kg in 10 minutes) given to six patients and one single oral dose (600 mg) given to the three others as well as to three of the patients who also received the two intravenous doses. RESULTS--With both intravenous and oral doses renin activity fell in 10 minutes to undetectably low values, while angiotensin II concentration fell overall by 80-90% with intravenous dosing and by 30-40% after the oral dose. Angiotensin II concentration was back to baseline four hours after the low and six hours after the high intravenous dose and remained low for at least eight hours after the oral dose. Blood pressure fell rapidly both after low and high intravenous doses and after the oral dose and remained low for hours. With the high intravenous dose the daytime (0900-2230), night time (2300-0600), and next morning (0630-0830) systolic blood pressures were significantly (p less than 0.05) lowered by 12.5 (95% confidence interval 5.6 to 19.7), 12.2 (5.4 to 19.3), and 10.7 (3.2 to 18.5) mm Hg respectively, and daytime diastolic pressure was lowered by 9.3 (2.2 to 16.8) mmHg. With the oral dose daytime, night time, and next morning systolic blood pressures were lowered by 10.3 (5.5 to 15.4), 10.5 (4.2 to 17.2), and 9.7 (4.0 to 15.6) mm Hg, and daytime and night time diastolic pressures were lowered by 5.8 (0.9 to 11.0) and 6.0 (0.3-12) mm Hg respectively. CONCLUSIONS--The effect of the inhibitor on blood pressure was maintained over a longer period than its effect on angiotensin II. RO 42-5892 is orally active and has a prolonged antihypertensive effect in patients who did not have sodium depletion. This prolonged effect seems to be independent, at least in part, of the suppression of circulating angiotensin II.

Cyclosporin A Impairs the Nocturnal Blood Pressure Fall in Renal Transplant Recipients

In renal transplant recipients, hypertension and a diminished nocturnal blood pressure fall are frequently found. To investigate whether this diminished nocturnal blood pressure fall is related to the use of cyclosporin A or to other factors, such as the use of glucocorticoids, we measured 24-hour ambulatory blood pressure in 18 renal transplant recipients both before and 16 weeks after conversion from cyclosporin A to azathioprine. Renal blood flow and glomerular filtration rate were estimated from 131I-hippurate and 125I-iothalamate clearances, respectively, and plasma concentrations of renin, atrial natriuretic peptide, norepinephrine, prostaglandin E2, and thromboxane B2 were determined. During cyclosporin A treatment, mean 24-hour blood pressure was 117 +/- 3 mm Hg, and the nocturnal fall in blood pressure was 4 +/- 9 mm Hg. A nondipping diurnal blood pressure pattern was present in 13 patients. After conversion to azathioprine, mean 24-hour blood pressure decreased to 109 +/- 3 mm Hg (P < .001), the nocturnal fall increased to 9 +/- 6 mm Hg, and the number of patients with a nondipping diurnal blood pressure pattern decreased to 9. The nocturnal fall in heart rate (17 +/- 10 beats per minute) during cyclosporin A did not change after conversion. Body weight and plasma concentrations of norepinephrine and renin did not change. Plasma concentrations of prostaglandin E2 and thromboxane B2 decreased after conversion, as did plasma atrial natriuretic peptide. Renal blood flow and glomerular filtration rate increased after conversion. In conclusion, cyclosporin A appears to be involved in the disturbance of the circadian blood pressure rhythm in renal transplant recipients. Although the precise mechanism is unclear. the elevated plasma atrial natriuretic peptide and slightly suppressed plasma renin concentrations suggest that intravascular volume expansion may contribute to the observed hemodynamic alterations.

Comparison between serum creatinine and creatinine clearance for the prediction of postoperative mortality in patients undergoing major vascular surgery.

BACKGROUND Poor renal function prior to surgery is associated with increased risk for mortality in patients undergoing major vascular surgery. Traditionally, this function is assessed by serum creatinine concentration (SeCreat). However, SeCreat is also influenced by age, gender and body weight. Hence, creatinine clearance (C(Cr)) is considered to be a better reflection of renal function. This study was undertaken to explore the prognostic value of preoperative calculated Cc, compared to SeCreat for the prediction of postoperative mortality. PATIENTS AND METHODS The study group comprised 852 consecutive patients who underwent elective major vascular surgery at the Erasmus Medical Center, Rotterdam. Preoperative C(Cr) was calculated based on the Cockroft-Gault equation using preoperative SeCreat, age, body weight and gender. Univariable logistic regression analyses were used to study the relation between preoperative SeCreat, C(Cr) and postoperative mortality. Furthermore, multivariable logistic regression analysis was applied to evaluate the additional predictive value of age, body weight and gender additional to SeCreat. The receiver operating characteristic (ROC) curve was determined to evaluate the predictive power of several regression models for perioperative mortality. RESULTS Postoperative mortality was 5.9% (50/852) within 30 days of surgery. In a univariable analysis, 10 micromol/l increment of SeCreat were associated with a 20% increased risk of postoperative mortality (OR = 1.2, 95% CI, 1.1-1.3) with an area under the ROC curve of 0.64 (95% CI, 0.56-0.71). If age, gender and body weight were added, the area under the ROC curve increased to 0.70 (95% CI, 0.63-0.77; p < 0.001), indicating that these risk factors had additional prognostic value. Indeed, in a separate regression analysis 10 ml/min decrease in C(Cr) was associated with a 40% increased risk of postoperative mortality (OR = 1.4,95% CI, 1.2-1.5; ROC area: 0.70, 95% CI, 0.63-0.76). ROC curve analysis showed that the cut-off value of 64 ml/min for C(Cr) yielded the highest sensitivity/specificity to predict postoperative mortality. CONCLUSION Preoperative SeCreat was strongly associated with postoperative mortality, and adding age, gender, and body weight to the model showed improved predictive power indicating that preoperative C(Cr) calculated with these data has additional prognostic value.

Hemodynamic and beta-adrenergic receptor adaptations during long-term beta-adrenoceptor blockade. Studies with acebutolol, atenolol, pindolol, and propranolol in hypertensive patients.

In an attempt to further clarify the mechanism of the maintenance of the antihypertensive effect of beta-adrenoceptor antagonists, the effects of four antagonists with different ancillary properties (acebutolol, atenolol, pindolol, and propranolol) on systemic and renal hemodynamics, body fluid volumes, hormones, and lymphocyte beta-adrenoceptor density were studied in four groups of 10 hypertensive patients. The patients were observed for 3 weeks during active treatment and for 2 weeks after withdrawal of treatment. At the end of the 3-week treatment period, the four drugs had an equal antihypertensive effect (fall in mean arterial pressure, 10-13%). Although renin activity was suppressed (60-70%) by all four drugs, changes in renin or pretreatment values of renin levels were not correlated with the fall in blood pressure. The drugs had no effect on plasma catecholamine concentrations or body fluid volumes. Despite similar antihypertensive effects among the four drugs, the changes in flow and resistance underlying the fall in blood pressure differed considerably. With pindolol, the fall in blood pressure was associated with a fall in vascular resistance (26 +/- 6%), whereas with propranolol, it was predominantly associated with a fall in cardiac output (11 +/- 7%). No significant changes in vascular resistance or cardiac output occurred with atenolol or acebutolol. The changes in renal blood flow and renal vascular resistance occurred in parallel with the changes in cardiac output and systemic vascular resistance. Plasma epinephrine concentration and pretreatment cardiac chronotropic responsiveness to isoproterenol appeared to be inversely correlated with lymphocyte beta-adrenoceptor density (Bmax) (r = -0.41 and -0.43, respectively). With pindolol, Bmax decreased maximally by 39 +/- 6%, and with propranolol, it increased by 51 +/- 17%. With both drugs, significant changes in Bmax were already present 24 hours after treatment. Furthermore, 1 week after withdrawal of treatment with pindolol, Bmax was still down-regulated, and cardiac chronotropic responsiveness was still decreased, whereas 1 week after withdrawal of propranolol, Bmax was still up-regulated, and cardiac chronotropic responsiveness was still increased. No changes in Bmax occurred with the beta 1-selective antagonists acebutolol and atenolol. Thus, despite an equal antihypertensive effect, the four beta-adrenoceptor antagonists appear to have dissimilar effects on cardiac output, renal blood flow, and lymphocyte beta-adrenoceptors. Changes in cardiac output, the circulating blood volume, or angiotensin-mediated vasoconstriction are factors unlikely to be crucial for the antihypertensive effect of beta-adrenoceptor antagonists. Therefore, interference with vasoconstrictor nerve activity through blockade of either central or peripheral prejunctional beta-adrenoceptors could be an alternative explanation of their blood pressure-lowering potential.

Abnormal diurnal variation of blood pressure, cardiac output, and vascular resistance in cardiac transplant recipients.

BackgroundAn attenuated or absent nocturnal decline in blood pressure has repeatedly been documented in cardiac transplant recipients. The present study was aimed at investigating the hemodynamic mechanism underlying this abnormality. Methods and ResultsIn 23 cardiac transplant recipients (11 to 36 months after transplantation) and in 23 control subjects matched for age and 24-hour mean arterial pressure, invasive 24-hour ambulatory blood pressure was measured by means of the Oxford technique. Beat-to-beat relative values of stroke volume were determined by means of a pulse-contour method, and relative changes of cardiac output (stroke volume × heart rate) and total peripheral vascular resistance (blood pressure/cardiac output) over the 24-hour period were calculated. The nocturnal decline in blood pressure was 20 ± 8% (mean ± SD) in control subjects but only 5 ± 9% (P < .001) in cardiac transplant recipients. In control subjects, the nocturnal decline in blood pressure was associated with a nocturnal fall in cardiac output of 24 ± 13%, whereas vascular resistance compared with daytime value did not change. The small nocturnal decline in blood pressure in cardiac transplant recipients was associated with an attenuated nocturnal fall in cardiac output of 14 ± 12% (P < .05 versus control subjects). In addition, vascular resistance compared with daytime value was increased by 9 ± 9% (P < .05) during the night. Both in cardiac transplant recipients and in control subjects, the nocturnal changes in blood pressure were correlated with the nocturnal changes in cardiac output but not with the nocturnal changes in total peripheral vascular resistance. ConclusionsThis study confirms the attenuated nocturnal fall in blood pressure in cardiac transplant recipients. Hemodynamically, this attenuated blood pressure decline is characterized by a reduced nocturnal fall in cardiac output, and it is associated with a nocturnal increase in vascular resistance.