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Biomedical subjects

O Lederballe

Publications and source records attributed to O Lederballe.

11 recordsLinked to original sources

Effect of antihypertensive treatment on cardiac and subcutaneous artery structure: a comparison between calcium channel blocker and thiazide-based regimens.

The effects of two antihypertensive regimens (isradipine and hydrochlorothiazide-amiloride) on the ratio between media thickness and lumen diameter of subcutaneous arteries and on left ventricular mass in essential hypertension were compared. Fifty patients, aged 46.3+/-8 (mean+/-SD) years, with newly diagnosed or poorly controlled essential hypertension were randomized to treatment with either isradipine or hydrochlorothiazide-amiloride. Atenolol and hydralazine were added in both groups as secondary and tertiary drugs, respectively, when needed for normalization of diastolic blood pressure. A subcutaneous gluteal biopsy was taken surgically before medication and again after 9 months of successful antihypertensive treatment. Two small resistance arteries were isolated from each biopsy and mounted in a Mulvany-Halpem isometric small vessel myograph. The media thickness-to-lumen diameter ratio (percentage) of the vessels was measured under standardized conditions and meaned. Left ventricular mass (LVM) index was determined by echocardiography according to the Penn convention. Ten patients were treated with isradipine as monotherapy, whereas only one patient was well controlled on diuretics as monotherapy. Mean blood pressure was reduced equally with the two regimens, from 131+/-9 mm Hg to 101+/-10 mm Hg with the isradipine and from 128+/-9 mm Hg to 99+/-7 mm Hg with the thiazide/atenolol regimen. LVM decreased significantly in both groups by 130+/-75 g with the isradipine-based regimen and by 70+/-53 g with the hydrochlorothiazide/atenolol-based regimen. The reduction of LVM was significantly greater on the isradipine-based regimen than on the thiazide-based regimen (P < .01). There was a significant reduction of media thickness-to-lumen diameter ratio during treatment with the isradipine-based regimen from 10.9% to 8.8% (P < .01). The reduction in the thiazide regimen was from 9.7% to 8.5%, which was not significant (P = .07). The study demonstrated significant reduction of hypertensive changes in peripheral resistance artery structure during antihypertensive treatment with an isradipine-based regimen. The thiazide/betablocker-based regimen did not have a significant effect on the vessels. Significant reduction of LVM was achieved with both isradipine-based and thiazide/atenolol-based regimens. The reduction of LVM obtained with the isradipine-based regimen was significantly greater than that of the thiazide/atenolol-based regimen.

Adult↗

Influence of humoral and neurohormonal factors on cardiovascular hypertrophy in untreated essential hypertensives.

In essential hypertension, cardiovascular structure is believed to be influenced by hormonal and by hemodynamic factors. The objective of the present study was, in essential hypertensives, to investigate the relationship between blood pressure (BP) level as well as circulating hormones on the one hand and cardiovascular structure on the other. Seventy-nine untreated essential hypertensives were examined by 24-h ambulatory BP monitoring, echocardiography, microscopy of subcutaneous resistance vessels and analyzes of plasma for angiotensin II (P-Ang II), aldosterone, atrial natriuretic factor and 24-h urinary excretion of catecholamines. Multiple regression analysis showed a statistically significant correlation between P-Ang II and the end diastolic interventricular septal diameter (IVSDd) (R = 0.32, P = .005) and a weak correlation between P-Ang II and the left ventricular posterior wall diameter (R = 0.22, P = .049). These correlations were closer in the subgroup of patients (N = 54) who had never received antihypertensive treatment (R = 0.42/0.32, respectively). A weak, though statistically significant, correlation was found between the catecholamine excretion and systolic BP (R = 0.26, P = .03). A statistically negative correlation existed between catecholamines and end-diastolic left ventricular internal diameter index (R = -0.36, P = .001). No significant relationship was found between hormonal levels and the tunica media structure of the resistance arteries. In conclusion, P-Ang II was in this study significantly correlated to IVSDd, but not to resistance artery structure. In essential hypertension a complex relationship exists between humoral and hemodynamic factors and cardiovascular remodeling.

Adult↗

Regression of media-to-lumen ratio of human subcutaneous arteries and left ventricular hypertrophy during treatment with an angiotensin-converting enzyme inhibitor-based regimen in hypertensive patients.

A total of 25 patients with newly diagnosed or poorly controlled essential hypertension were randomly selected from a larger group referred to hospital. Treatment was initiated with perindopril (4-8 mg orally). If normotension was not achieved, isradipine (5-10 mg orally) was added and, if necessary, hydralazine was added. Before treatment and at the end of a 9-month period of normotension (diastolic blood pressure < or = 90 mm Hg), 24-hour blood pressure and echocardiographic measurements were performed and resistance artery structure was determined. A total of 20 age- and sex-matched normotensives were used as controls. During antihypertensive treatment, mean blood pressure was reduced from 128 +/- 11 to 103 +/- 6 mm Hg. Left ventricular mass was reduced from 300 +/- 76 to 198 +/- 54 g. The media:lumen ratio of the resistance arteries decreased from 9.8 +/- 2.6% to 7.8 +/- 1.9%; control subjects exhibited a media:lumen ratio of the same magnitude (7.9 +/- 2.0%). Results indicate that a perindopril-based regimen is extremely efficient in normalizing resistance artery and cardiac ventricular structures within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension still remains to be demonstrated.

Analysis of Variance↗

The relation between peripheral vascular structure, left ventricular hypertrophy, and ambulatory blood pressure in essential hypertension.

The relations between left ventricular mass (LVM), peripheral resistance artery structure, and ambulatory BP were studied in 83 patients with previously untreated or poorly regulated essential hypertension and 20 healthy controls of similar age and sex. LVM was assessed by echocardiography. Signs of left ventricular hypertrophy (LVH) were present in 67 (81%) of the patients and in none of the controls. Peripheral resistance arteries were isolated from surgical gluteal skin biopsies and mounted in a Mulvany-Halpern isometric small vessel myograph, and their media:lumen ratio, media thickness, and media cross-sectional area were determined under standardized conditions. Mean (+/- SD) ambulatory BP was 122 +/- 9 mm Hg among patients and 96 +/- 8 mm Hg among controls (P < .001). LVM was 327 +/- 99 g among patients and 197 +/- 37 g among controls (P < .001). Media thickness of resistance arteries was 21.0 +/- 4.2 microns among hypertensives and 16.2 +/- 2.6 microns among controls (P < .001). The media:lumen ratio of arteries from patients was 10.2 +/- 2.6% v 7.9 +/- 2.0% in arteries of similar internal diameter from controls (P < .01). Both LVM index (LVMI) and media/lumen ratio correlated significantly with BP. There was significant correlation between media:lumen ratio and LVMI among hypertensive patients (r = 0.45, P < .001), but if patients were subdivided according to the presence of LVH this correlation was found only among patients with LVH (r = 0.60 P< .001) and not among patient without LVH nor controls. Multiple regression analyses of age, body surface area, media/lumen ratio, and BP on LVM or LVMI revealed independent contributions of media/lumen ratio and BP. Age had no influence in the models. Similar results were obtained when casual BP was replaced with ambulatory BP in these analyses. No correlation was found between LVMI and media cross-sectional area. A minor subset of patients with complete absence of nocturnal BP drop had particularly great LVM and media:lumen ratio. The study suggests that cardiac and arteriolar tissue undergo parallel structural remodeling in essential hypertension.

Adult↗

Normalization of structural cardiovascular changes during antihypertensive treatment with a regimen based on the ACE-inhibitor perindopril.

Untreated essential hypertension is associated with left ventricular hypertrophy (LVH) and structural changes in resistance vessels. The aim of this study was to establish the effect of perindopril based antihypertensive therapy on media thickness to lumen diameter (media:lumen) ratio of peripheral resistance vessels and left ventricular mass in essential hypertension. Twenty-five patients with newly diagnosed or poorly regulated essential hypertension were treated with perindopril. Insufficient treatment response (DBP > 90 mmHg) led to addition of isradipine, and hydralazine was used as a tertiary drug if necessary. Gluteal subcutaneous biopsies were taken surgically at baseline and after 9 months of successful treatment. Two small resistance arteries were isolated and mounted in a small vessel myograph, and media:lumen ratio (%) was measured under standardized conditions. Left ventricular mass was determined by echocardiography. Mean (SD) media:lumen ratio decreased from 9.8 (2.6) % to 7.8 (1.9) % (p < 0.05), while left ventricular mass decreased from 299 (75) g to 199 (53) g (p < 0.001). Correlation was found between changes in left ventricular mass index and media:lumen ratio (r = 0.62, p < 0.01). It is concluded that a perindopril based regimen efficiently normalizes resistance artery structure and left ventricular hypertrophy in essential hypertension within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension remains to be investigated.

Adult↗

Aggressive long-term antihypertensive therapy with pinacidil does not cause regression of cardiovascular hypertrophy in the spontaneously hypertensive rat.

After dosage titration from the age of 1 month to the age of 3 months, spontaneously hypertensive rats (SHR) were treated with pinacidil 10 mg/kg daily until the age of 6 or 12 months. Morphometric data were obtained from the treated SHR as well as from untreated age-matched SHR and normotensive Wistar-Kyoto rats (WKY) at these two developmental stages. Heart:body weight ratios and media:lumen ratios for resistance vessels were determined. Vessels obtained from the mesenteric region were investigated on a myograph. Vessels from heart, kidney and lung were investigated by morphometric analysis of histological sections, only specimens from 12-month-old rats were used. In SHR no effects of either ageing or treatment were detectable, although their blood pressure had been effectively held at normotensive levels throughout the life of the treated animals from the age of 3 months. With the exception of the media index of the pulmonary vessels, which was not statistically different from treated or control SHR, the WKY morphological parameters were significantly lower. In conclusion, pinacidil normalized blood pressure without complications, but this did not affect SHR cardiovascular structure. It is suggested that development of this strain-specific enlargement can only be modified if blood pressure is kept at hypotensive levels, or if the effect of a hitherto unidentified causative factor is antagonized by more-specific pharmacological treatment.

Animals↗

A novel principle for detection of systolic and diastolic blood pressure tested in man and rat with special reference to its applicability in rat studies.

A non-invasive procedure for the application of a photodetector method in rat studies to obtain both systolic and diastolic blood pressure measurements is described. The method has been tested against well-established procedures in rats and in human beings and has proved sufficiently fast and reliable for use in long-term studies. Regression analysis of simultaneously obtained invasive versus non-invasive measurements yielded correlation coefficients of 0.99 and 0.98 respectively. Comparison with the Korotkoff principle in human beings yielded correlation coefficients of 0.96 and 0.78 respectively.

Animals↗

Treatment with hydralazine in mild to moderate mitral or aortic incompetence.

Twenty-two patients with mild or moderate mitral or aortic incompetence were randomly assigned to treatment with either hydralazine (mean 127 mg/day, range 37-225) or placebo. Eight patients in the hydralazine group and ten patients in the placebo group completed the study. Two of the patients in the hydralazine group and one patient in the placebo group were withdrawn because of suspected side effects. One patient dropped out because of influenza. Over a period of seven weeks the patients were monitored clinically as well as non-invasively with echocardiography and exercise testing. The systolic blood pressure fell from 152 +/- 10 to 135 +/- 9 mm Hg (mean +/- s.e.m.) (17%, P less than 0.01). The diastolic blood pressure fell from 63 +/- 8 to 58 +/- 8 mm Hg (5%, P = 0.09). The heart rate was unchanged. Left ventricular internal diameter in systole decreased from 49 +/- 3 to 45 +/- 3 mm (9%, P = 0.05) and in diastole from 73 +/- 4 to 70 +/- 3 mm (4%, P = 0.03). Left ventricular systolic wall tension fell from 200 +/- 16 to 152 +/- 18 mm Hg (24%, P less than 0.01). Left ventricular shortening fraction increased from 32 +/- 3 to 36 +/- 3% (12%, P less than 0.01). Maximal exercise capacity improved from 3200 +/- 800 to 3800 +/- 700 kpm (19%, P = 0.02). No significant responses were observed in the placebo group. Oral hydralazine reduces left ventricular internal diameters, improves left ventricular performance, presumably at a lower level of oxygen consumption, and improves exercise capacity in patients with modest mitral or aortic incompetence.

Adult↗

Myocardial ischemia and ventricular arrhythmias in relation to left ventricular mass and resistance artery structure.

The study comprised 83 patients, mean (+/-SD) age 47 +/- 8 years, with essential hypertension. Systolic and diastolic blood pressure at inclusion were 171 +/- 16 and 110 +/- 7 mm Hg, respectively. Two small resistance arteries were dissected from a subcutaneous gluteal biopsy and mounted in an isometric small vessel myograph for measurement of the media:lumen ratio. Left ventricular mass (LVM) was estimated by echocardiography, and the occurrence of ventricular arrhythmias was assessed by ambulatory ECG for 48 h. Left ventricular hypertrophy (LVH) occurred in 67% of the patients. Systolic function was generally unimpaired. ST depression was found in 75%, and ventricular arrhythmias in 45%. Twenty-two patients had permanent ST depression, and they had also greater LVM and more frequent ventricular arrhythmias than those without permanent ST depression. The area under the ST trend curve of all significant ST depressions was correlated to the LVM (r = 0.42, p < 0.001). Patients with arrhythmias had significantly greater area under the ST trend curve of all significant ST depressions than patients without arrhythmias (p < 0.05). In patients with LVH and permanent ST depression, the media:lumen ratio of the peripheral vessels was greater than that of patients with LVH but without permanent ST depression (11.6 +/- 2.9 vs. 9.8 +/- 2.0, p < 0.01). This suggests that hypertensive structural changes similar to those observed in peripheral vessels might occur in the walls of myocardial resistance arteries.

Adult↗