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Biomedical subjects

T Hedner

Publications and source records attributed to T Hedner.

At least 109 records · Page 6Linked to original sources
PubMed1997

The Captopril Prevention Project (CAPPP) in hypertension--baseline data and current status.

The Captopril Prevention Project (CAPPP) is an ongoing intervention study conducted in 11,019 hypertensive patients in Sweden and Finland. Patients have been randomized to receive either conventional antihypertensive therapy (diuretics and/or beta-blockers) or captopril-based treatment. A prospective, randomized, open, blinded-endpoint evaluation (PROBE) study design is used to compare these two therapeutic regimens as regards cardiovascular morbidity and mortality. The rationale for the CAPPP Study are the many observations of beneficial effects of ACE inhibition, as compared to diuretics and beta-blockers, on intermediary endpoints such as insulin sensitivity, serum lipoproteins, left ventricular hypertrophy and renal function. Captopril has also been shown to be markedly effective in the treatment of left ventricular dysfunction as well as congestive heart failure. The hypothesis is that these differences might result in improved risk reduction when ACE inhibitors are used in the treatment of hypertension. The present paper describes the baseline data and the changes in blood pressure during the first year in the total cohort. During the first year the average blood pressure was reduced by 11/8 mm Hg. A number of substudies have been conducted in the CAPPP Study. In one of these insulin sensitivity was compared in a subgroup of the patients using the euglycemic insulin clamp technique. In another substudy the ACE gene was sequenced and some new polymorphisms were discovered. Several other substudies are in progress or in the planning phase. The main results of the CAPPP Study should be available by mid-1998. Some of the intended anayses of the final results as well as other planned substudies are briefly described here.

Adult↗
PubMed1997

The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group.

The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity, largely due to a decreased incidence of stroke, whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies. Furthermore, treated hypertensive patients still have a higher cardiovascular complication rate, compared with matched normotensives. This is particularly evident in patients with left ventricular hypertrophy (LVH), a major independent risk indicator for cardiovascular disease. In addition to elevating blood pressure, angiotensin II (A-II) exerts an important influence on cardiac structure and function, stimulating cell proliferation and growth. Thus, to further reduce morbidity and mortality when treating hypertensive patients, it may be important to effectively block the effects of A-II. This can be achieved directly at the A-II receptor level by losartan, the first of a new class of antihypertensive agents. It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy, and thus improves prognosis. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients (initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg) with electrocardiographically documented LVH. The study, which will continue for at least 4 years and until 1,040 patients experience one primary endpoint, has been designed with a statistical power that will detect a difference of at least 15% between groups in the incidence of combined cardiovascular morbidity and mortality. It is also the first prospective study with adequate power to link reversal of LVH to reduction in major cardiovascular events. The rationale of the study, which will involve more than 800 clinical centers in Scandinavia, the United Kingdom, and the United States, is discussed, and the major features of its design and general organization are described. On April 30, 1997, when inclusion was stopped, 9,218 patients had been randomized.

Adrenergic beta-Antagonists↗
PubMed1997

Physician and patient evaluation of hypertension-related risks and benefits from treatment.

Implementation of management programmes in hypertension in accordance with current guidelines needs the participation not only of physicians and other health professionals, but also of the patients themselves. Patients' knowledge of, and attitudes to, cardiovascular risk factors, as well as patients' perceptions of the benefits and potential risks of treatment, are factors likely to be of importance regarding their compliance, their opinions and their acceptance of treatment. The extent to which patients are able to assess the absolute and relative risks of having hypertension, as well as individual benefits from treatment, is yet largely unexplored. Compared with a number of common drug treatments, the general adult population perceives the risks from receiving antihypertensive drug therapy as intermediate to low. Improving patients' knowledge and acceptance of antihypertensive therapy by improving the physician-patient relationship will involve patients more in their own treatment decisions, thereby probably improving the management and treatment as a whole.

Adult↗
PubMed1997

Measures of endothelial function as an endpoint in hypertension?

The vascular endothelial cell is a multipotent cell which has several functions: transport barrier, phagocytosis, coagulation/anticoagulation, fibrinolysis, autocrine/paracrine and metabolic functions. The release of vasoactive agents, such as the vasodilators EDRF (NO) and EDHF, and vasoconstrictors, such as endothelin (ET), represents an important local mechanism altering the balance of vasodilation/ vasoconstriction of the vascular smooth muscle cell. Inhibition of the synthesis of NO by exogenous (e.g. L-NAME) or endogenous (e.g. ADMA) L-arginine analogues may cause transient or sustained hypertension. A similar effect may be achieved by continuous administration of the potent vasoconstrictor ET. Endothelial dysfunction, associated with a deficient NO production and release as well an enhanced ET generation, may be present in some forms of vascular disease, such as hypertension, atherosclerosis, diabetes mellitus or sleep apnea. Whether such alterations may be a cause of hypertension and involved in the maintenance of high blood pressure or whether they represent a consequence of the hypertensive disease remains to be concluded. Furthermore, while there is emerging evidence that endothelial dysfunction in cardiovascular disease may be reversed by therapy, it remains to be determined whether measures of endothelial function in man may serve as predictors for morbidity or mortality.

Endothelium, Vascular↗
PubMed1996

Neuropeptide Y potentiates noradrenaline-induced contraction through the neuropeptide Y Y1 receptor.

To elucidate which neuropeptide Y receptor subtype is responsible for the neuropeptide Y-induced potentiation of the noradrenaline-evoked contraction in human omental arteries we used antisense oligodeoxynucleotide (Antisense), the new selective neuropeptide Y Y1 receptor antagonist, BIBP3226 {(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl) methyl]-D-arginine-amide} and the reverse transcriptase-polymerase chain reaction (RT-PCR). Neuropeptide Y significantly potentiated the noradrenaline-induced contraction in non-incubated vessels (pEC50 6.4 +/- 0.2 vs. 5.9 +/- 0.2) and in vessels incubated with 1 microM Sense oligodeoxynucleotide (Sense) (pEC50 6.0 +/- 0.1 vs. 5.6 +/- 0.2). In vessels incubated with 1 microM Antisense the potentiating effect of neuropeptide Y was completely abolished. BIBP3226 (1 microM) inhibited the neuropeptide Y-induced potentiation in human omental arteries (pEC50 5.8 +/- 0.3 vs. 6.4 +/- 0.2). Finally, messenger RNA for the neuropeptide Y Y1 receptor was detected using RT-PCR. On the basis of our results we conclude that the neuropeptide Y-induced potentiation of the noradrenaline-induced contraction is mediated by the neuropeptide Y Y1 receptor.

Adrenergic alpha-Agonists↗
PubMed1996

Diabetes mellitus and raised serum triglyceride concentration in treated hypertension--are they of prognostic importance? Observational study.

OBJECTIVE: To analyse whether metabolic changes during long term treatment with antihypertensive drugs are associated with an increased risk of coronary heart disease. DESIGN: Observational study. SETTING: Gothenburg, Sweden. SUBJECTS: 686 middle aged hypertensive men, recruited after screening of a random population sample, and followed for 15 years during treatment with predominantly beta adrenoceptor blockers or thiazide diuretics, or both. Coronary heart disease and diabetes mellitus were registered at yearly patient examinations. Entry characteristics, as well as within study serum concentrations of cholesterol and triglycerides and the development of diabetes mellitus, were related to the incidence of coronary heart disease in a time dependent Cox's regression analysis. MAIN OUTCOME VARIABLE: Coronary heart disease morbidity. RESULTS: Diabetes mellitus, raised serum cholesterol and triglyceride concentrations present at the beginning of the study were all significantly predictive of coronary heart disease in univariate analysis. The relative risk of diabetes mellitus and of a 1 mmol/l increase in the cholesterol and triglyceride concentrations was 2.12 (95% confidence interval 1.11 to 4.07), 1.21 (1.05 to 1.39), and 1.21 (1.03 to 1.43) respectively. However, when the within study metabolic variables were analysed, only the serum cholesterol concentration was significantly and independently associated with coronary heart disease (relative risk 1.07 (1.02 to 1.13)). Although the triglyceride concentrations increased slightly during the follow up, the within study serum triglyceride concentrations were not associated with the incidence of coronary heart disease (1.04 (0.96 to 1.10)). New diabetes mellitus-that is, onset during follow up-was not significantly associated with an increased risk for coronary heart disease (1.48 (0.37 to 6.00)). CONCLUSIONS: Metabolic disturbances such as diabetes mellitus and hyperlipidaemia presenting before the start of antihypertensive treatment have a prognostic impact in middle aged, treated hypertensive men. Moreover, while within study cholesterol concentration was an independent predictor of coronary heart disease, drug related diabetes mellitus and raised serum triglyceride concentrations that are associated with treatment do not seem to have any major impact on the coronary heart disease prognosis in this category of patients.

Adrenergic beta-Agonists↗
PubMed1996

Lisinopril reduces postexercise albuminuria more effectively than atenolol in primary hypertension.

Physical exercise causes transient albuminuria. The mechanisms of postexercise albuminuria are not fully clarified but stimulation of the reninangiotensin system (RAS) probably plays a major role through intrarenal haemodynamic changes causing an elevated filtration pressure. In a randomised, double-blind, crossover study we compared the effects on urinary albumin excretion (UAE) of lisinopril (L) and atenolol (A) therapy, i.e. we aimed to investigate whether inhibition of the RAS or inhibition of beta1-adrenoceptor-mediated effects of the sympathetic nervous system differed with regard to changes in UAE. Sixteen patients with uncomplicated primary hypertension were studied. Four standardised bicycle ergometer exercise tests were performed, before and after each active treatment period. UAE 30 min postexercise, determined by radioimmunoassay, was significantly lowered by both treatments: -278 mu g center dot min-1 (L) and -199 mu g center dot min-1 (A). The reduction of postexercise UAE achieved by treatment with the angiotensin-converting enzyme (ACE) inhibitor (L) was significantly greater than that achieved by the beta1-selective adrenoceptor blocker treatment. Blood pressure (BP) at rest and during exercise were equally reduced by both drugs. In conclusion, this study showed that antihypertensive treatment with an ACE inhibitor was more effective in reducing exercise-induced albuminuria than a beta1-selective adrenoceptor-blocking agent with a similar degree of BP reduction in patients with uncomplicated primary hypertension. This suggests that the RAS plays a major role in postexercise albuminuria in hypertensive subjects. The clinical significance of this finding, however, remains to be clarified.

Adrenergic beta-Antagonists↗
PubMed1996

Postoperative analgesic effects of an external cooling system and intra-articular bupivacaine/morphine after arthroscopic cruciate ligament surgery.

The aim of this study was to evaluate the analgesic effect of an external cooling system with or without the combined effect of intra-articularly administered bupivacaine/morphine after arthroscopic anterior cruciate ligament (ACL) reconstruction. Fifty patients with isolated ACL insufficiency operated on under general anaesthesia were randomized to three different postoperative treatment groups. Group I was treated with the cooling system during the first 24 h after surgery and an intra-articular injection of 20 ml of physiological saline given at the completion of surgery; in group II, the cooling system was combined with an intra-articular injection of 20 ml bupivacaine 3.75 mg/ml and 1 mg of morphine at the end of the operation; while group III (placebo group) received an intra-articular injection of 20 ml of physiological saline at the completion of surgery. Pain was assessed using a visual analogue scale (VAS) at 1, 2, 4, 6, 24 and 48 h postoperatively. Supplementary analgesic requirements were registered. In group I 80% (16/20) and in group II 90% (18/20) of the patients were satisfied with the postoperative pain control regimen (NS). This was significantly better than in group III, where 30% (3/10) were satisfied. The pain scores were significantly lower in the two treatment groups compared with the placebo group during the entire postoperative period. The pain score was significantly lower in group II than in group I at 24 and 48 h after surgery. The supplementary analgesic requirements were also lower in the two treatment groups compared with the placebo group. No complications due to the use of the cooling system or the intra-articular injections of bupivacaine/morphine were observed. The external cooling system used in this study provides an effective method of obtaining pain relief after arthroscopic surgery. The combination with an intra-articular injection of morphine and bupivacaine results in a slightly greater analgesic effect than the cooling system alone.

Adolescent↗
PubMed1996

Effects of atrial natriuretic peptide on acute renal impairment in patients with heart failure after cardiac surgery.

OBJECTIVE: To investigate the effects of IV infusion of atrial natriuretic peptide (human ANP 1-28) on renal function in patients with acute heart failure and renal impairment after cardiac surgery. DESIGN: Pharmocodynamic dose-effect investigation. SETTING: Cardiothoracic Intensive Care Unit of a university hospital. PATIENTS: Twelve patients (mean age 68 years, range 44-78 years) treated with inotropic drugs and an intra-aortic balloon pump (n = 8) were studied 1-3 days after cardiac surgery. Patients had acute renal impairment, defined as a rise in serum creatinine of more than 50% compared to preoperative values. Patients were receiving dopamine and furosemide infusion to increase urine flow. INTERVENTIONS: Baseline measurements of glomerular filtration rate (GFR) and renal blood flow (51Cr-EDTA and PAH clearance) were first performed during two 30-min periods. ANP was then administered for two consecutive 30-min periods (25 and 50 ng/kg per min), followed by two control periods. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure decreased by 6% at the highest ANP dose. Urine flow, GFR and RBF increased 62%, 43% and 38%, respectively, while renal vascular resistance decreased 30%. At this dose level, circulating ANP concentrations were on the average eight fold higher than preinfusion levels. CONCLUSIONS: ANP improved renal function and decreased elevated renal vascular resistance in patients with renal dysfunction after cardiac surgery. The improvement in renal blood flow and glomerular filtration rate may be of potential therapeutic value to prevent or treat exaggerated renal vasoconstriction in patients with acute renal impairment following cardiac surgery.

Acute Kidney Injury↗
PubMed1996

Haemodynamic effects and pharmacokinetics of oral d- and l-nebivolol in hypertensive patients.

OBJECTIVE: Nebivolol is a selective beta 1-adrenergic receptor blocker possessing an ancillary vasodilating effect. The objective of the present study was to study the haemodynamic and pharmacokinetic properties of nebivolol 5 mg once daily in a double-blind, placebo-controlled cross-over study. METHODS: Fifteen patients, 12 men and 3 women, with essential hypertension were investigated. Blood pressure and peripheral circulation were determined after acute oral nebivolol administration, 5 mg daily, and after 4 weeks treatment. RESULTS: The acute effect on blood pressure upon single-dosing was weak and non-significant. After 4 weeks both systolic blood pressure (152 vs 163 mmHg) and diastolic blood pressure (89 vs 97 mmHg) were significantly reduced after nebivolol treatment as compared to placebo. Following the first dose the venous volume was higher on placebo (5.88 ml.100 ml-1 tissue) as compared to active nebivolol treatment (5.17 ml.100 ml-1 tissue), while there were no statistically significant differences with regard to venous plethysmographic findings after 1 month on placebo (5.53 ml.100 ml-1 tissue) or on active treatment (5.97 ml.100 ml-1 tissue). Calculated peripheral resistance did not differ between active treatment (617 units) or placebo (548 units) after the first dose, whereas it was significantly lowered after 4 weeks of nebivolol treatment (483 units) as compared to placebo (593 units). CONCLUSIONS: Oral nebivolol 5 mg once daily lowered blood pressure and heart rate during steady state compared to placebo. Moreover, venous volume was reduced during acute but not steady-state dosing, while peripheral resistance was unaffected in the acute phase but reduced during steady state. Plasma concentrations of the separate enantiomers plus hydroxylated metabolites after the first and last dose in hypertensive patients were similar to those in healthy subjects.

Adrenergic beta-Antagonists↗
PubMed1996

Nitric oxide in the oxygenator sweep gas reduces platelet activation during experimental perfusion.

BACKGROUND: Hemorrhage is a major complication experienced in 10% to 35% of neonates treated with extracorporeal life support (ECLS). The increased bleeding tendency is partly due to an ECLS-induced thrombocytopenia and impaired platelet function. In the present study, we evaluated the effect of nitric oxide on the ECLS-induced platelet consumption and activation. METHODS: Two identical in vitro ECLS circuits were primed with fresh, heparin-treated human blood and circulated for 24 hours. Nitric oxide (15, 40, or 77 ppm) was added to one of the oxygenators in each pair. Eight paired experiments were performed. Platelet count, plasma beta-thromboglobulin, platelet serotonin content, plasma nitrate, plasma cyclic guanosine monophosphate, and platelet membrane glycoprotein Ib were assayed before the start and at 0.5, 1, 3, 12, and 24 hours of perfusion. RESULTS: Plasma nitrate and plasma cyclic guanosine monophosphate levels were significantly higher in the nitric oxide circuits than in the control circuits (p < 0.01). Higher platelet counts (p < 0.01) and lower beta-thromboglobulin levels (p < 0.01) were observed in the nitric oxide circuits compared with the control circuits. However, no significant differences in platelet serotonin content or platelet membrane glycoprotein Ib density were noted between the circuits. CONCLUSIONS: Nitric oxide probably reduces platelet consumption and platelet activation during ECLS.

Analysis of Variance↗
PubMed1996

Increased levels of endothelin-1 in bronchoalveolar lavage fluid of patients with lung allografts.

The aim of the present study was to determine levels of endothelin-1 in bronchoalveolar lavage fluid and in plasma in patients with lung and heart-lung allografts. The aim was based on the hypothesis that levels of endothelin-1 are elevated in the bronchoalveolar lavage fluid of patients with lung allografts. Patients (n = 23) undergoing heart-lung (n = 8), single-lung (n = 10), or bilateral lung (n = 5) transplantation were included in the study. In patients with single-lung allografts, endothelin-1 levels were analyzed in bronchoalveolar lavage fluid from both the transplanted and the nontransplanted, native lung. The level of endothelin-1 was also analyzed in bronchoalveolar lavage fluid from 12 patients who did not undergo transplantation. Transbronchial biopsies and bronchoalveolar lavage were done routinely or when clinically indicated on 64 different occasions, between 2 and 104 weeks after transplantation. The level of endothelin-1 was measured in bronchoalveolar lavage fluid and plasma by radioimmunoassay. Immunoreactive endothelin-1 was detectable in bronchoalveolar lavage fluid from all patients. The concentration of endothelin-1 in bronchoalveolar lavage fluid from transplanted lungs (2.94 +/- 0.30 pg/ml, n = 64) was significantly higher compared with that in bronchoalveolar lavage fluid from patients without allografts (0.86 +/- 0.20 pg/ml, n = 12, p < 0.01). In patients who received single-lung transplantation because of emphysema, the level of endothelin-1 in bronchoalveolar lavage fluid from the transplanted lung was significantly greater than that from the native lung (5.61 +/- 1.9 versus 0.39 +/- 0.05 pg/ml, p < 0.05). Concentrations of endothelin-1 in bronchoalveolar lavage fluid did not correlate with grade of rejection, infection, or time after transplant. Plasma levels of endothelin-1 were unchanged with pulmonary rejection. These results indicate that endothelin-1 is released into bronchi of transplanted human lungs. The release is not associated with rejection or infection. Because of its potent mitogenic properties, endothelin-1 may have a potential impact in the development of posttransplant complications such as bronchiolitis obliterans.

Adult↗
PubMed1996

Concentrations of morphine and morphine metabolites in CSF and plasma during continuous subcutaneous morphine administration in cancer pain patients.

Plasma and cerebrospinal fluid (CSF) steady-state concentrations (Css) of morphine (M) and the main metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), were determined by high performance liquid chromatography (HPLC) in 21 cancer patients treated with chronic subcutaneous morphine infusion. There was a moderate, but statistically significant correlation between the daily dose of morphine and the concentrations of morphine, M3G and M6G in CSF. A poorer correlation to concentrations were seen in plasma. The mean +/- SEM CSF/plasma morphine concentration ratio was 0.36 +/- 0.07. In plasma and CSF, the mean steady state concentration of M3G but not M6G substantially exceeded that of morphine where the mean CSF M/M3G/M6G ratio was 1:15:0.5 (molar basis), and the mean plasma ratio was M/M3G/M6G 1:31:3 (molar basis). The mean M3G and M6G concentrations in CSF were approximately 8 and 10% of those found in plasma, but there was a wide interindividual variation. Plasma concentrations of both morphine glucuronides were positively correlated to serum creatinine. Neither pain intensity, evaluated by visual analogue scale (VAS), nor side effects showed any relationship to the CSF M3G concentrations, M3G/M or the M3G/M6G ratios. We conclude that during steady state subcutaneous administration of morphine, there is a large interindividual variation in plasma morphine with poor relationship to the daily administered dose. In CSF this correlation was more evident. Plasma and CSF concentrations of M3G and CSF concentrations of M6G correlated with administered morphine dose. There was an accumulation of both morphine glucuronides in patients with elevated serum creatinine. Measurements of morphine, M3G and M6G in CSF did not show any overt relationship to analgesia or side effects.

Aged↗
PubMed1996

Substance P-induced respiratory excitation is blunted by delta-receptor specific opioids in the rat medulla oblongata.

The effects of substance P (SP) and the naturally occurring met-enkephalin and the synthetic mu-specific opioid agonist, DAGO (Tyr-D-Ala-Gly-N-Methy-Phe-Gly-ol) and the delta-specific opioid agonist DADL (Tyr-D-Ala-Gly-Phe-D-Leu) on basal ventilation were investigated in halothane-anaesthetized rats. Local injections of SP (0.75-1.5 nmol) in the ventrolateral medulla oblongata (VLM), e.g. nucleus paragigantocellularis, and nucleus reticularis lateralis increased ventilation because of an elevation of tidal volume. Met-enkephalin induced a short-lasting ventilatory depression mainly because of a depression of tidal volume. Activation of delta- and mu-opioid receptors in the VLM by local application of DADL and DAGO, respectively, induced ventilatory depression, which was later in onset and more long-lasting. Local administration of met-enkephalin into the VLM also produced a long-lasting inhibition of the SP-induced ventilatory excitation. A similar blockade of the SP-induced excitatory ventilatory response could be elicited by DADL but not by DAGO. This antagonistic effect was attenuated by local application of the delta-opioid receptor antagonist ICI 154. 129. We conclude that the naturally occurring met-enkephalin as well as synthetic mu- and delta-specific enkephalin analogues (DAGO and DADL, respectively) in VLM depress basal ventilation by an effect on inspiratory drive. There is a functional antagonism between activation of delta-opioid receptors and SP receptors into the VLM in respect to respiratory regulation.

Analgesics, Opioid↗
PubMed1996

Myocardial circulatory and metabolic effects of atrial natriuretic peptide after coronary artery bypass grafting.

The purpose of this study was to examine the effects of incremental infusion rates of human atrial natriuretic peptide (ANP), 25, 50, 100 ng.kg-1. min-1, on myocardial blood flow and metabolism (n = 10), and to compare the effects of ANP on these variables with those of equipotent infusion rates of sodium nitroprusside (SNP) (n = 9) 1-3 h after coronary artery bypass grafting (CABG). ANP induced a dose-dependent decrease in mean arterial blood pressure and systemic vascular resistance. There were no changes in cardiac index, heart rate, or cardiac filling pressures. ANP caused no changes in myocardial blood flow or its distribution, and caused no changes in myocardial oxygen extraction. Regional myocardial lactate uptake (RMLU) and extraction (RMLE) increased significantly (P < 0.05) at 50 ng.kg-1.min-1 (10.2 +/- 3.8 mumol/min and 8.2% +/- 3.0%, respectively) as compared to control (-1.1 +/- 3.0 mumol/min and -1.3% +/- 3.3%, respectively). RMLE and RMLU were significantly (P < 0.05) higher with ANP (5.7% +/- 2.5% and 6.8 +/- 3.7 mumol/min, respectively) compared to SNP (-1.5% +/- 2.1% and -0.1 +/- 3.7 mumol/min, respectively). We conclude that ANP has no dilatory effects on coronary vascular resistance vessels and thus lacks the potential to maldistribute flow, and that ANP improves myocardial lactate metabolism after CABG.

Atrial Natriuretic Factor↗
PubMed1996

The Diltiazem Different Doses Study--a dose-response study of once-daily diltiazem therapy for hypertension.

The objective was to evaluate the dose-related efficacy/tolerance profile of 240, 300, 360, and 420 mg diltiazem slow-release, once-daily (OD) doses, with emphasis on the 300 mg dose. The study was randomized and double-blinded with a 36-week parallel, two-branched, cross-over design after a single-blind, run-in period of 4 weeks on placebo and 6 weeks on 300 mg diltiazem OD. Each branch included six 6-week active treatment periods with 180, 240, and 300 mg tablets, one or two tablets OD. Participants were men and postmenopausal women, aged 40-70 years, with uncomplicated primary hypertension (WHO stages I and II) and a supine diastolic blood pressure of 95-115 mm Hg in the absence of antihypertensive medication. A total of 138 patients from various clinics participated in the study. All were included in the intention to treat analysis, and 117 patients were included in the per protocol analysis. Criteria for evaluation were blood pressure, heart rate, and response rate, as well as plasma diltiazem and metabolite M1 concentration before morning dose. Well-being of the patients and adverse events were recorded. Electrocardiogram and standard laboratory tests were obtained. Analysis of variance was used for statistical calculations. Supine blood pressures and response rates in the per protocol analysis were 161.2/97.0 for placebo (29.1%), 155.2/ 92.8 for 240 mg (54.7%), 153.8/91.6 for 300 mg (55.6%), 155.5/92.0 for 360 mg (59.0%), and 152.0/90.5 for 420 mg (63.2%) of diltiazem OD. The intention to treat analysis was very similar to the per protocol analysis. There was a small but statistically significant decrease in heart rate for all doses of diltiazem OD compared to placebo. A linear relationship existed between the dose and the plasma concentration of both diltiazem and metabolite M1, as well as a dose-response relationship. Diltiazem OD in the dose range 240-420 mg was generally well tolerated and not differently perceived from the placebo treatment except for ankle edema (2-6%). The study shows that OD diltiazem is significantly superior to placebo for mild to moderate hypertension and that the effect is large enough to be clinically valuable. It also shows that there is a linear dose-response relationship for diltiazem between 240 and 420 mg.

Adult↗