Is apoptosis an important pathogenic factor in cardiovascular disease?
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Apoptosis↗
Biomedical subjects
L Gullestad
Publications and source records attributed to L Gullestad.
[Mortality and morbidity after coronary bypass surgery in high-risk patients].
A total of 113 women and 912 men were submitted to coronary artery bypass surgery at Surgical Department A, Rikshospitalet between August 1982 and December 1986 and followed till January 1993. We found no difference in early mortality, recurrent angina pectoris or non-fatal myocardial infarction in diabetic patients compared to nondiabetic patients. However, total mortality was 1.87 times higher in the diabetic group. For patients with ejection fraction < or = 40%, early mortality was 10.2 times higher than for the reference group. For total mortality we found a practically linear relationship between increased mortality and falling ejection fraction values. We found no relationship between ejection fraction and recurrent angina and non-fatal myocardial infarction, neither did we find any difference in mortality and morbidity between women and men. Although a somewhat higher mortality and morbidity rate must be expected for high-risk patients, they seem to profit to the same extent from the favourable effects of coronary bypass surgery as other patients.
Adult↗
Clinical, hemodynamic, and cardiopulmonary exercise test determinants of survival in patients referred for evaluation of heart failure.
BACKGROUND: Accurate prognosis in chronic heart failure has become increasingly important in assessing the efficacy of treatment and in appropriately allocating scarce resources for transplantation. Previous studies of severe heart failure have been limited by short follow-up periods and few deaths. OBJECTIVE: To establish clinical, hemodynamic, and cardiopulmonary exercise test determinants of survival in patients with heart failure. DESIGN: Retrospective study. SETTING: Hospital-based outpatient heart failure clinic. PARTICIPANTS: 644 patients referred for evaluation of heart failure over 10 years. MEASUREMENTS: Age, cause of heart failure, body surface area, cardiac index, ejection fraction, pulmonary capillary wedge pressure, left ventricular dimensions, watts achieved during exercise, heart rate, maximum systolic blood pressure, and oxygen uptake (VO2) at the ventilatory threshold and at peak exercise were measured at baseline. Univariate and multivariate analyses were done for clinical, hemodynamic, and exercise test predictors of death. A Cox hazards model was developed for time of death. RESULTS: During a mean follow-up period of 4 years, 187 patients (29%) died and 101 underwent transplantation. Actuarial 1-year and 5-year survival rates were 90.5% and 73.4%, respectively. Resting systolic blood pressure, watts achieved, peak VO2, VO2 at the ventilatory threshold, and peak heart rate were greater among survivors than among nonsurvivors. Cause of heart failure (coronary artery disease or cardiomyopathy) was a strong determinant of death (relative risk for coronary artery disease, 1.73; P< 0.01). By multivariate analysis, only peak VO2 was a significant predictor of death. Stratification of peak VO2 above and below 12, 14, and 16 mL/kg per minute demonstrated significant differences in risk for death, but each cut-point predicted risk to a similar degree. CONCLUSIONS: Peak VO2 outperforms clinical variables, right-heart catheterization data, exercise time, and other exercise test variables in predicting outcome in severe chronic heart failure. Direct measurement of VO2 should be included when clinical or surgical decisions are being made in patients referred for evaluation of heart failure or those considered for transplantation.
Adult↗
[Thrombolytic treatment in acute myocardial infarction. Choice of preparations in Norwegian hospitals].
In 1994 Statens legemiddelkontroll recommended Norwegian hospitals to increase the use of recombinant tissue plasminogen activator (r-tPA) in thrombolytic treatment of acute myocardial infarction. Using a questionnaire, which was distributed to all medical departments in Norwegian hospitals, we examined and assessed the preference of thrombolytic agents. None of the coronary care units administered r-tPA routinely as their first choice. Of 59 hospitals involved, 35 (59%) considered r-tPA on a wider indication (i.e. young age, short history of symptoms, and anterior wall infarction) than the 24 (41%) that only used r-tPA when streptokinase had recently been given. Of a total of 11,191 cases of myocardial infarction in 1996, 628 (6%) were treated with r-tPA. Closer examination of 2,818 cases of myocardial infarction in 13 hospitals revealed that thrombolytic treatment was given in 1,016 (36%) instances. In 206 cases (20%), the chosen agent was r-tPA, whereas 810 (80%) were given streptokinase. The reasons for the preference of streptokinase to r-tPA are discussed.
Cardiology Service, Hospital↗
Effect of heart transplantation on impaired peripheral microvascular perfusion and reactivity in congestive heart failure.
Whether reduced peripheral blood flow in congestive heart failure is reversed after heart transplantation, has not been closely examined. We therefore studied skin microvascular resting perfusion and reactivity in patients pre- and postoperatively. Resting digital skin perfusion, together with the responses to cold pressor test, postocclusive reactive hyperemia and direct skin heating were examined with laser Doppler perfusion measurements. We examined 28 patients with congestive heart failure and 14 of these patients after heart transplantation and compared them to 13 healthy controls. Measurements were performed within 3 months preoperatively and 12 days, 1, 2, 3 and 6 months postoperatively. Patients with congestive heart failure had significantly lower resting perfusion levels than controls and demonstrated attenuated responses to both stimuli of vasodilation (all P<0.01). While peak hyperemic responses improved significantly after transplantation, postocclusive area under the hyperemic curve decreased further, and none of these variables were normalized after 6 months. In contrast, minimal perfusion during cold pressor test increased from a significantly lower level in the patients with congestive heart failure (P<0.05), to a level similar to that of the controls within 12 days postoperatively. Thus, skin microvascular perfusion and reactivity improve, but are not normalized within 6 months of transplantation. Both pre- and postoperative factors may be involved in maintaining a dysfunction of the peripheral microcirculation, which may contribute to exercise intolerance and hypertension in heart transplant recipients.
Adult↗
Neuropeptide Y receptor 1 (NPY-Y1) expression in human heart failure and heart transplantation.
Neuropeptide Y (NPY) is a neurotransmitter released from cardiac sympathetic nerve terminals along with catecholamines. It influences vascular tone and cardiac function, probably through the receptor subtype Y1. The present study examined the expression of Y1 in patients with end-stage heart failure and in heart transplant recipients. Y1 mRNA was analyzed in right ventricular endomyocardial biopsies taken from 12 donor hearts prior to implantation (controls), 15 patients with end stage heart failure at time of transplantation, and 16 patients more than 1 year after transplantation. RT-PCR (reverse transcription polymerase chain reaction) was used to detect mRNA for the Y1 receptor, the beta1-adrenergic-receptor, and beta-actin. Y1 mRNA was present in biopsies of all donor hearts, but was observed significantly less frequently in the two patient groups; only 5 out of 15 (P < 0.01) heart failure and 9 out of 16 (P < 0.05) transplant recipients demonstrated visible PCR product. In contrast, mRNA for the beta1-adrenergic receptor and beta-actin were detected by RT-PCR in all samples. Our results provide the first evidence for altered regulation of the neuropeptide Y1 receptor in heart failure and transplant patients, and suggests that loss of signal transduction by this receptor may be adaptive in both groups.
Actins↗
Elevated circulating levels of C-C chemokines in patients with congestive heart failure.
BACKGROUND: Immunologic and inflammatory responses appear to play a pathogenic role in the development of congestive heart failure (CHF). Activation and migration of leukocytes to areas of inflammation are important factors in these immunologic responses. Because the C-C chemokines are potent chemoattractants of monocytes and lymphocytes and can modulate other functions of these cells (eg, generation of reactive oxygen species), we measured circulating levels of three C-C chemokines in CHF. METHODS AND RESULTS: Levels of macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein- 1alpha (MIP-1alpha), and RANTES (regulated on activation normally T-cell expressed and secreted) were measured by enzyme immunoassays in 44 patients with CHF and 21 healthy control subjects. CHF patients had significantly elevated levels of all chemokines with the highest levels in New York Heart Association class IV, and MCP-1 and MIP-1alpha levels were significantly inversely correlated with left ventricular ejection fraction. Elevated C-C chemokine levels were found independent of the cause of the heart failure, but MCP-1 levels were particularly raised in patients with coronary artery disease. Studies on cells isolated from peripheral blood suggested that platelets, CD3+ lymphocytes, and in particular, monocytes, might contribute to the elevated C-C chemokine levels in CHF. The increased MCP-1 levels in CHF were correlated with increased monocyte activity reflected in an enhancing effect of serum from CHF patients on O2-generation in monocytes, which was inhibited by neutralizing antibodies against MCP-1. CONCLUSIONS: This first demonstration of increased circulating levels of C-C chemokines in CHF with particularly high levels in patients with severe disease may represent previously unrecognized pathogenic factors in CHF.
Adult↗
Levels of circulating adhesion molecules in congestive heart failure and after heart transplantation.
Recent reports suggest a role for immunologic and inflammatory processes in the pathogenesis of congestive heart failure (CHF) and accelerated coronary artery disease (CAD) after heart transplantation (HT). The interaction between endothelial cells, leukocytes, and platelets involving various adhesion molecules may be of particular importance. We therefore measured serum levels of soluble(s) vascular cell adhesion molecule-1 (VCAM-1), sP-selectin, and sE-selectin in 34 patients with severe CHF (23 with CAD and 11 with idiopathic dilated cardiomyopathy) and in 20 healthy controls. Twenty of the patients were followed with serial measurements of these circulating adhesion molecules (CAMs) for up to 2 years after HT. Levels of all 3 CAMs were significantly elevated in patients with CHF compared with controls irrespective of the etiology of heart failure, with particularly high concentrations of sVCAM-1. After HT, different patterns in CAMs were found over time. Whereas there was a normalization of sE-selectin levels after HT, concentrations of sVCAM-1 also declined, but without normalization. In contrast, sP-selectin levels were persistently elevated, with the highest concentrations at the end of the study period. The persistent elevation of sP-selectin and the lack of normalization of sVCAM-1 levels were associated with persistently raised serum levels of tumor necrosis factor-alpha, and these findings were not related to either acute episodes of allograft rejection or intercurrent infections. These results support the notion that immunologic and inflammatory processes are important features of CHF. Furthermore, the persistently elevated levels of CAMs and tumor necrosis factor-alpha found up to 2 years after HT may reflect a state of persistent immune activation in these patients, possibly involved in the development of CAD after HT.
Adolescent↗
Serial exercise testing and prognosis in selected patients considered for cardiac transplantation.
OBJECTIVES: This study sought to examine the predictive value of variables obtained from serial maximal exercise testing, echocardiography, and ejection fraction in patients referred as potential heart transplant candidates. BACKGROUND: Variables such as peak VO2, left ventricular dimensions, ejection fraction, and hemodynamic measurements are known to predict prognosis in heart failure, but there are few data on the impact of serial measurements of these variables on subsequent mortality. METHODS AND RESULTS: Two hundred sixty-three ambulatory patients with severe heart failure referred as potential candidates for heart transplantation who underwent two exercise tests (mean 7.8 months apart) after optimal medical treatment were identified. At the same two time points, echocardiography was performed in 106 (37%) and ejection fraction was measured in 84 (30%). During a mean follow-up period of 3.9+/-0.1 years, 70 (25%) died and 45 (19%) underwent heart transplantation. Exercise capacity, peak exercise heart rate, and peak exercise systolic blood pressure achieved were all significantly higher among survivors compared with nonsurvivors. Among the survivors a slight increase in peak VO2 and ejection fraction were observed, but there were no significant differences in the changes of any of the measured variables between survivors and nonsurvivors. There were no significant differences in survival between patients with increased versus those with decreased peak VO2, left ventricular dimensions, or ejection fraction. CONCLUSION: Although peak VO2, left ventricular dimensions, and ejection fraction predict survival, changes in these parameters do not add any prognostic information in patients with severe heart failure who have been stabilized with optimal medical treatment. Routine use of these procedures therefore does not seem to be warranted and should be performed only in the context of a specific clinical situation. Serial measurements of these parameters do not appear to be useful in the risk stratification of patients referred for heart transplantation.
Case-Control Studies↗
Angiotensin II receptor subtype AT1 and AT2 expression after heart transplantation.
OBJECTIVE: Cardiac hypertrophy appears early after heart transplantation, and may represent a myocardial response to injury. Recent evidence suggests that angiotensin II (Ang II) may promote growth through the AT1 and inhibit growth through the AT2 receptor subtypes. We therefore asked whether hypertrophy after heart transplantation is characterized by alterations in Ang II receptor gene expression. METHODS: The expression of Ang II receptor subtypes. AT1 and AT2, was analyzed in right ventricular endomyocardial biopsies taken from 10 human donor hearts prior to implantation (controls) and from 17 heart transplant recipients, 11 studied during annual evaluation (> 1 year after transplantation) and 6 one week after transplantation. Competitive reverse transcription polymerase chain reaction (RT-PCR) was performed using synthetic RNA internal standards for both receptor subtypes. RESULTS: AT1 and AT2 receptor mRNAs were detected in all samples. AT1 receptor mRNA decreased 4.5 fold (p < 0.01) and AT2 receptor mRNA 4.2 fold (p < 0.001) in transplant patients compared with controls. In the subgroup of patients examined one week after surgery AT1 was reduced relative to AT2 receptor mRNA, resulting in an altered ratio of AT1 to AT2 early after transplantation. There was no correlation between Ang II receptor levels and left ventricular wall thickness, and the decrease in receptor level did not correlate with any hemodynamic parameters, cyclosporine blood levels, or plasma renin, Ang II or pANP, except for a negative correlation between AT2 mRNA and plasma renin (r = -0.49, p = 0.05). CONCLUSIONS: Contrary to our expectations, mRNA for both Ang II receptors was downregulated after heart transplantation. The cause of myocardial hypertrophy after heart transplantation is still unclear, but the hypertrophy does not appear to be driven by increased transcription of the AT1 receptor.
Adult↗
Exercise capacity and hormonal response in adults with childhood onset growth hormone deficiency during long-term somatropin treatment.
Growth hormone (GH) deficiency in adults in associated with reduced muscular strength and peak oxygen uptake (peak Vo2). How these variables are influenced by long-term somatropin therapy in adults with childhood onset GH-deficiency has not been precisely defined. The effect of somatropin treatment in 20 childhood onset GH-deficient adults on muscular strength, maximal exercise capacity, and hormonal response to exercise were therefore examined in a double-blind placebo-controlled study with recombinant human GH (rhGH, 12 microg/kg/day) for 6 months, followed by 36 months of open-labeled uninterrupted therapy, after which treatment was stopped for 9 months. After 6 months of treatment, exercise capacity increased significantly, as assessed by time to exhaustion [mean change (95% CI) 0.8 (0.2, 1.4) min, P<0.05], total (accumulated) work [11.6 (0.8, 22.4) kJ, P<0.05] and peak Vo2 [2.6 (0.3, 4.9) ml/kg/min, P<0.01], whereas no significant changes were observed during placebo. This effect on exercise capacity remained unchanged during long-term somatropin treatment, mainly due to increased capacity among patients with isolated GH deficiency. Nine months after stopping treatment, peak Vo2 decreased by 11% from 32.8+/-2.5 to 29.1+/-2.1 ml/kg/min (P<0.05). Maximal muscular handgrip strength was not affected by treatment. Long-term GH therapy resulted in decreased respiratory exchange value (R value) at rest and during exercise (P<0.001), suggesting a metabolic role with increased fat combustion. Resting and submaximal noradrenaline levels decreased during somatropin treatment (P<0.05), while no effect was observed for other exercise-induced hormonal responses, including adrenaline, insulin, prolactin, renin, and ACTH. We conclude that somatropin therapy to childhood onset GH deficient adults has a favourable effect on exercise capacity and may have a potentially beneficial effect on plasma catecholamines.
Adolescent↗
Exercise capacity in heart transplant recipients: relation to impaired endothelium-dependent vasodilation of the peripheral microcirculation.
OBJECTIVES: The aim of this study was to examine the responses to endothelium-dependent and -independent vasodilators on the peripheral microcirculation in heart transplant recipients in relation to exercise capacity compared with that in healthy controls. BACKGROUND: Impaired endothelium-dependent vasodilation of the microcirculation may play an important role in the limitation of exercise capacity after heart transplantation. METHODS: Microvascular perfusion responses to four graded levels of iontophoretically applied 1% acetylcholine (endothelium-dependent vasodilator) and 1% sodium nitroprusside (SNP) (endothelium-independent) in the forearm skin of 42 transplant recipients and 16 age-matched controls were determined by laser Doppler perfusion measurements. Maximal exercise capacity was assessed by peak oxygen uptake (peak VO2) during progressive, symptom-limited, upright bicycle exercise. RESULTS: With similar baseline perfusion levels in transplant recipients and controls (4.2 +/- 0.4 vs 4.6 +/- 0.6 arbitrary units [AU]), the increases in perfusion to acetylcholine, but not to SNP, were significantly attenuated in the transplant recipients: 7.0 +/- 1.0 vs 11.0 +/- 2.0, 12.7 +/- 1.5 vs 21.0 +/- 2.8, 21.0 +/- 1.9 vs 32.7 +/- 2.4, and 28.0 +/- 1.6 vs 39.2 +/- 2.4 AU, respectively (all p < 0.01). Peak VO2 was significantly lower in the transplant recipients (22.4 +/- 1.0 vs 38.0 +/- 2.9 ml/kg/min; p < 0.01). Furthermore, acetylcholine responses of the transplant recipients correlated closely to their peak VO2, irrespective of level of application (r = 0.63; p < 0.001, all four acetylcholine responses taken together), whereas no such correlation was found for SNP responses. In the control group, no relation was observed in acetylcholine/SNP responses to peak VO2. CONCLUSIONS: Exercise limitation in transplant recipients appears strongly associated with attenuated endothelium-dependent vasodilation of the peripheral microcirculation.
Acetylcholine↗
The role of exercise testing and gas-exchange measurement in the prognostic assessment of patients with heart failure.
Functional impairment has long been recognized as an important factor in the risk paradigm among patients with heart disease. In chronic heart failure, this issue has been even more important in recent years because of the steady growth in the number of patients awaiting heart transplantation relative to the available pool of donor hearts. The use of gas-exchange techniques to assess patients with heart failure has attracted interest because these techniques provide a more precise, reproducible, objective, and physiologic expression of exercise tolerance. Numerous studies published in the 1990s demonstrate that maximal oxygen uptake (peak VO2) is an independent predictor of mortality in patients with heart failure. Achievement of a peak VO2 that is less than 14 mL/kg/min has been recognized as one of the relative indications for transplantation, because patients who achieve a measurement that is higher than 14 mL/kg/min have a 1-year mortality rate similar to that of patients who undergo transplantation (i.e., > 90%). However, some debate exists regarding the optimal cutpoint that separates survivors from nonsurvivors, and studies have not consistently defined the timing of the test relative to optimization of medical therapy. It has also been debated which hemodynamic variables, at rest or during exercise, should be used in combination with peak VO2 to optimally stratify risk in these patients. This article reviews the applications of cardiopulmonary exercise testing in prognosis among patients with chronic heart failure.
Chronic Disease↗
Endothelium-dependent vasodilation of the skin microcirculation in heart transplant recipients.
Patients with heart failure demonstrate attenuated endothelium-dependent vasodilation of the peripheral circulation, while this is suggested to be reversed after heart transplantation. However, data from human subjects are limited and conflict with studies on the peripheral vasomotor tone in cyclosporine-treated animals, suggesting endothelial dysfunction. We recorded forearm skin perfusion responses following graded iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent) by laser Doppler perfusion measurements in 32 heart transplant recipients and 15 age-matched controls. In addition, the hyperemic response to 3 min of blood flow occlusion to the forearm was measured on the third finger pulp. With comparable baseline values, the increases in perfusion to the 4 applications of acetylcholine were significantly attenuated in heart transplant recipients compared with controls: 59 +/- 9 vs. 146 +/- 32, 242 +/- 39 vs. 492 +/- 77, 480 +/- 66 vs. 845 +/- 120 and 699 +/- 77 vs. 993 +/- 139% (mean +/- SEM; all p < 0.01). Peak hyperemia (134 +/- 4 vs. 153 +/- 12 arbitrary units (AU); p < 0.05)), time for the hyperemic perfusion to return to preocclusive baseline (52.4 vs. 102.9 s; p < 0.01) and hence the area under the perfusion curve (1469 +/- 244 vs. 4581 +/- 921 AU s; p < 0.01) were reduced among heart transplant recipients. The area under the perfusion curve correlated significantly with mean arterial blood pressure (r = -0.60; p < 0.01) and with the responses to iontophoresis of acetylcholine (r = 0.41; p < 0.01). Two non-invasive tests of vascular function demonstrate attenuated endothelial-dependent microvascular responses in heart transplant recipients. The relative impact of prior congestive heart failure and postoperative factors, such as treatment with cyclosporine, remains to be determined.
Acetylcholine↗
AT1 and AT2 angiotensin receptor gene expression in human heart failure.
BACKGROUND: The availability of selective antagonists for angiotensin II receptors has focused interest on the gene expression of angiotensin II-receptor subtypes in the human heart. METHODS AND RESULTS: We analyzed expression of the AT1 and AT2 subtypes of the angiotensin II receptor in ventricular myocardium taken from 9 donor hearts before implantation and from 12 patients with heart failure (6 with dilated cardiomyopathy and 6 with ischemic heart disease). Competitive reverse transcription-polymerase chain reaction with synthetic RNA internal standards was used to detect mRNA for both subtypes and to quantify relative differences in levels between failing and non-failing ventricular myocardium. AT1- and AT2-receptor mRNA could be detected in all samples. AT1-receptor gene expression was 2.5-fold greater in nonfailing hearts than in patients with failing hearts (P = .015). There was no significant difference in AT2-receptor mRNA expression in failing and nonfailing hearts. CONCLUSIONS: The level of expression of the angiotensin AT1 receptor appears to decrease in the failing human ventricle whereas the level of AT2 expression is unaffected. These changes parallel the changes found in human ventricular myocardium at the receptor level, suggesting that the changes in receptor level may result from changes in gene expression or mRNA stability.
Adult↗
Outcome of bypass surgery in patients with chronic ischemic left ventricular dysfunction. Predictive value of MR imaging.
PURPOSE: To determine the preoperative findings of MR imaging of the left ventricle (LV) that could best predict the functional outcome of the LV after surgical revascularization. MATERIAL AND METHODS: Patients with angina pectoris, previous myocardial infarction, and dysfunction of the LV, and who had a preoperative cine MR, were re-evaluated after bypass surgery with MR in a study on the effects of revascularization after mean 22 months. RESULTS: Angina pectoris was relieved in all patients except one, but the maximum workload during the exercise test was increased in only 3 patients. Coronary angiography showed that 37 of 45 (82%) of the distal anastomoses were open. The LV ejection fraction was the same before and after operation both at angiography and MR imaging. MR showed LV end-diastolic volume to be increased from 190 +/- 50 ml to 250 +/- 70 ml. Compared to angiography, MR provided additional information regarding myocardial wall thickness and function, and the size of myocardial infarction. Improvement in systolic wall thickening was seen in 65% of the segments that had had an end-diastolic wall thickness (EDWT) greater than 15 mm before operation, while only 4% of the segments with EDWT < 6 mm improved. In the wall thickness range of 6-15 mm, MR was unable to predict the functional outcome of the LV. CONCLUSION: Preoperative MR findings of thick myocardial walls with poor function seem predictive of improved function after revascularization. When the LV wall thickness is less than 6 mm, no improvement should be expected.
Aged↗
Gas exchange and neurohumoral response to exercise: influence of the exercise protocol.
Maximal oxygen uptake varies with the exercise protocol, but the extent to which hormonal and metabolic responses to exercise are influenced by the exercise protocol has not been precisely defined. Twelve healthy subjects underwent maximal exercise testing using two incremental bicycle tests with individualized, identical work rate increments between 40 and 70 W. One protocol employed a 1-min and the other a 3-min duration per stage. Expiratory gas and venous blood were sampled at regular intervals for metabolic and hormonal analysis. Exercise duration for the 1-min and 3-min protocols was 6.0 +/- 0.1 and 14.3 +/- 0.3 min, respectively (P < 0.001). Significantly higher values were observed for peak VO2 and maximal ventilation during the 3-min protocol compared with the 1-min protocol (41.1 +/- 1.8 vs 38.3 +/- 1.6 ml.kg-1.min-1, P < 0.001; and 104.9 +/- 8.0 vs 97.2 + 5.7 l.min-1, P < 0.05, for peak VO2 and peak ventilation, respectively). However, the maximal workload achieved was higher during the 1-min versus the 3-min protocol (330 + 24 vs 280 + 21 W, P < 0.01). No differences were observed for maximal heart rate or blood pressure, whereas maximal plasma lactate was roughly twice as high during the 3-min compared with the 1-min protocol (7.5 +/- 0.8 vs 3.8 +/- 0.5 mmol.l-1, P < 0.001). Norepinephrine, epinephrine, dopamine, and growth hormone levels were generally higher throughout exercise during the 3-min compared with the 1-min protocol. When expressed as a percentage of peak VO2, however, differences in catecholamine levels were not observed. Endothelin levels did not change. We conclude that the exercise protocol profoundly influences exercise capacity as well as the metabolic and hormonal response to exercise and should be considered when using these variables to evaluate an intervention.
Adult↗
Post-transplant hyperlipidaemia: low-dose lovastatin lowers atherogenic lipids without plasma accumulation of lovastatin.
OBJECTIVES: The purpose of the present study was twofold. First, to determine the frequency of hyperlipidaemia after heart transplantation (Tx) in relation to values obtained before Tx. Secondly, to examine the effect of low-dose lovastatin on possible antiatherogenic mechanisms and test the hypothesis that the side-effects are dose-dependent. SUBJECTS AND DESIGN: Retrospective study of the frequency of hyperlipidaemia disturbances in heart transplant patients. In addition, in a prospective study, the safety and efficacy of incremental low doses of lovastatin up to 20 mg day-1 were studied, with measurements of its plasma concentration in 24 cyclosporin A treated heart (n = 14) and kidney (n = 10) recipients with total cholesterol > 7.5 mmol L-1. RESULTS: Cholesterol increased markedly after heart transplantation from a pretransplant value of 5.3 (5.0,5.6) mmol L-1 to 6.7 (6.4,7.0) mmol L-1 after 1 year and then remained constant, but this increase was largely due to a 'normalization' since cholesterol decreased significantly during increasing heart failure before transplantation. Treatment with lovastatin decreased total cholesterol by 19% (P < 0.001), primarily by an effect on LDL cholesterol. HDL cholesterol increased by 15% (P < 0.05), whereas triglycerides remained unchanged. Lovastatin also caused a significant reduction in apolipoprotein B of 16%, and lipid peroxidation of 40%, whereas apolipoprotein A-I, fibrinogen, and glycerol were unchanged. Plasma concentration of lovastatin was significantly higher in transplant recipients compared with controls, but there was no accumulation during incremental dosing of lovastatin. The drug was well tolerated without significant symptoms or evidence of myopathy. CONCLUSIONS: Hyperlipidaemia is common after cardiac transplantation. Treatment with low dose lovastatin is well tolerated and has a favourable effect on atherogenic lipids.
Adult↗