Biomedical subjects

J Hartikainen

Publications and source records attributed to J Hartikainen.

At least 19 recordsLinked to original sources

PubMed2001

Anthracycline-induced cardiomyopathy: long-term effects on myocardial cell integrity, cardiac adrenergic innervation and fatty acid uptake.

Cardiotoxicity of anthracyclines is a clinical challenge in cancer chemotherapy. Limited data is available on the physiological mechanisms responsible for anthracycline-induced heart failure or its recovery. We studied four patients with a history of severe anthracycline-induced heart failure manifested 2-116 months earlier by using radionuclide ventriculography for the measurement of left ventricular function, indium-111-antimyosin scintigraphy for the detection of myocardial cell injury and iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy for the assessment of cardiac adrenergic innervation. Myocardial perfusion and fatty acid utilization were assessed with iodine-123-paraphenyl pentadecanoid acid (pPPA) and single photon emission computed tomography (SPECT). Symptoms of congestive heart failure (CHF) were still present in two patients whereas the others were asymptomatic at the time of the study. The patients who showed complete clinical recovery had normal or near normal left ventricular ejection fraction (LVEF) (47 and 52%), whereas the patients with symptoms of heart failure had low ejection fractions (21 and 31%). All patients presented with abnormal antimyosin uptake and decreased myocardial MIBG uptake. Patients with low ejection fraction tended to have higher antimyosin uptake suggesting more severe, persistent myocyte injury. All but one patient showed normal fatty acid utilization. These data suggest that patients with a history of severe anthracycline-induced cardiomyopathy have persistent myocardial cell injury and adrenergic dysfunction up to 10 years after the development of heart failure. These findings seem to be present regardless of recovery of left ventricular function.

3-Iodobenzylguanidine↗

PubMed2001

Comparison of echocardiography and radionuclide ventriculography in the follow-up of left ventricular systolic function in adult lymphoma patients during doxorubicin therapy.

OBJECTIVES: To compare echocardiography (ECHO) and radionuclide ventriculography (RVG) in the monitoring of left ventricular systolic function during doxorubicin therapy in adult lymphoma patients. DESIGN: Prospective study. SETTINGS: University hospital. SUBJECTS: A total of 28 adult patients who received doxorubicin to a cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: ECHO and RVG were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: At baseline, the mean (+/-SE) left ventricular ejection fractions (LVEF) were 58 +/- 1.3, 71 +/- 1.8 and 58 +/- 1.7% as determined by RVG, M-mode ECHO and two-dimensional (2D) ECHO, respectively. After the cumulative doxorubicin dose of 500 mg m(-2) LVEF decreased to 49.6 +/- 1.7% (RVG) (P < 0.001), 62 +/- 1.6% (M-mode) (P=0.006) and 52.5 +/- 1.3% (2D ECHO) (P=0.036). Although a significant correlation between LVEF determined by RVG and M-mode ECHO (r=0.615, P=0.002) and a trend between RVG and 2D ECHO (r=0.364, P=0.096) were observed, there were substantial differences in the results of individual patients. In the agreement analysis using the method of Bland and Altman there was a mean difference of 12% units with the upper limit of agreement +26% units and the lower limit of agreement -2.1% units for LVEF determinations with M-mode ECHO and RVG, and a mean difference of 3.3% units with upper and lower limits of agreement +19.6 and -13.1% units for LVEF determinations with 2D ECHO and RVG, respectively. CONCLUSION: We found only a moderate agreement between left ventricular systolic function determined by ECHO and RVG methods. Thus, in the follow-up of left ventricular function in adult patients during doxorubicin therapy, the guidelines based on LVEF measurement by RVG cannot be applied to ECHO. Consequently, RVG remains the method of choice in this context.

Adult↗

PubMed2001

The effects of gender and age on the colonoscopic examination.

The data concerning the influence of gender and age on a patient's toleration of and the technical difficulty of colonoscopy are conflicting. One hundred eighty patients (108 women and 72 men) undergoing colonoscopy were categorized into three age groups: the young (aged 2040 years), the middle-aged (aged 41-60 years), and the old (aged 61-75 years). The endoscopists assessed the examination immediately after the procedure. The patients completed a questionnaire before leaving the endoscopy unit and again 2 weeks later. The women rated colonoscopy after the procedure more painful (p < 0.01) and in the repeat questionnaire more painful (p < 0.05) and more difficult (p < 0.05) than men. Also, the endoscopists judged colonoscopy to be more difficult (p < 0.001) and the time taken to reach cecum longer (p < 0.01) for women. The young experienced more discomfort than the middle-aged or the old, as evaluated after the procedure (p < 0.05). In the repeat questionnaire, the young reported more discomfort and pain than the middle-aged (p < 0.05). The endoscopists also judged the examination to be more difficult and the time taken to intubate cecum longer for the old than for the middle-aged (p < 0.05) or the young (p < 0.01). Correspondingly, the examination time was shorter among the young when compared with the middle-aged (p < 0.05) or the old (p < 0.001). The young were least willing to repeat the examination (p < 0.05). Colonoscopy is less tolerable and more difficult for women. Although colonoscopy among the old patients was technically more difficult, they tolerated the procedure better than the young.

Age Factors↗

PubMed2000

Intravascular adenovirus-mediated VEGF-C gene transfer reduces neointima formation in balloon-denuded rabbit aorta.

BACKGROUND: Gene transfer to the vessel wall may provide new possibilities for the treatment of vascular disorders, such as postangioplasty restenosis. In this study, we analyzed the effects of adenovirus-mediated vascular endothelial growth factor (VEGF)-C gene transfer on neointima formation after endothelial denudation in rabbits. For comparison, a second group was treated with VEGF-A adenovirus and a third group with lacZ adenovirus. Clinical-grade adenoviruses were used for the study. METHODS AND RESULTS: Aortas of cholesterol-fed New Zealand White rabbits were balloon-denuded, and gene transfer was performed 3 days later. Animals were euthanized 2 and 4 weeks after the gene transfer, and intima/media ratio (I/M), histology, and cell proliferation were analyzed. Two weeks after the gene transfer, I/M in the lacZ-transfected control group was 0. 57+/-0.04. VEGF-C gene transfer reduced I/M to 0.38+/-0.02 (P:<0.05 versus lacZ group). I/M in VEGF-A-treated animals was 0.49+/-0.17 (P:=NS). The tendency that both VEGF groups had smaller I/M persisted at the 4-week time point, when the lacZ group had an I/M of 0.73+/-0.16, the VEGF-C group 0.44+/-0.14, and the VEGF-A group 0. 63+/-0.21 (P:=NS). Expression of VEGF receptors 1, 2, and 3 was detected in the vessel wall by immunocytochemistry and in situ hybridization. As an additional control, the effect of adenovirus on cell proliferation was analyzed by performing gene transfer to intact aorta without endothelial denudation. No differences were seen in smooth muscle cell proliferation or I/M between lacZ adenovirus and 0.9% saline-treated animals. CONCLUSIONS: Adenovirus-mediated VEGF-C gene transfer may be useful for the treatment of postangioplasty restenosis and vessel wall thickening after vascular manipulations.

Adenoviridae↗

PubMed2000

Catheter-mediated vascular endothelial growth factor gene transfer to human coronary arteries after angioplasty.

Blood vessels are among the easiest targets for gene therapy. However, no data are available about the safety and feasibility of intracoronary gene transfer in humans. We studied the safety and efficacy of catheter-mediated vascular endothelial growth factor (VEGF) plasmid/liposome (P/L) gene transfer in human coronary arteries after percutaneous translumenal coronary angioplasty (PTCA) in a randomized, double-blinded, placebo-controlled study. The optimized angioplasty/gene delivery method was previously shown to lead to detectable VEGF gene expression in human peripheral arteries as analyzed from amputated leg samples. Gene transfer to coronary arteries was done with a perfusion-infusion catheter, using 1000 microg of VEGF or beta-galactosidase plasmid complexed with 1000 microl of DOTMA:DOPE liposomes. Ten patients received VEGF P/L, three patients received beta-galactosidase P/L, and two patients received Ringer lactate. Gene transfer to coronary arteries was feasible and well tolerated. Except for a slight increase in serum C-reative protein in all study groups, no adverse effects or abnormalities in laboratory parameters were detected. No VEGF plasmid or recombinant VEGF protein was present in the systemic circulation after the gene transfer. In control angiography 6 months later, no differences were detected in the degree of coronary stenosis between treatment and control groups. We conclude that catheter-mediated intracoronary gene transfer performed after angioplasty is safe and well tolerated and potentially applicable for the prevention of restenosis and myocardial ischemia.

Adult↗

PubMed2000

Cardiac adrenergic denervation in patients with non-Q-wave versus Q-wave myocardial infarction.

In spite of smaller infarct size and better preserved left ventricular function the long-term prognosis after a non-Q-wave infarction is not better than after a Q-wave infarction. In fact, the risk of sudden cardiac death is higher in patients with a non-Q-wave infarction than in patients with a Q-wave infarction. One possible reason for postinfarction arrhythmias is cardiac adrenergic denervation resulting from myocardial infarction. In this study we compared cardiac adrenergic innervation after non-Q-wave and Q-wave infarctions. Single-photon emission tomography using iodine-123 metaiodobentzylguanidine (MIBG) and technetium-99m sestamibi (MIBI) tracers were conducted in order to compare cardiac adrenergic denervation and myocardial perfusion in 12 patients with a non-Q-wave infarction and 15 patients with a Q-wave infarction. MIBG and MIBI defects were determined as regional uptake < or = 30% of maximal myocardial activity. The size of MIBI defects calculated as a percentage of left ventricular mass was significantly smaller in patients with a non-Q-wave infarction than in patients with a Q-wave infarction (4%+/-3% vs 9%+/-7%, P<0.05, respectively). According to the maximal serum creatine kinase activity, less myocardium was damaged in patients with a non-Q-wave infarction than in patients with a Q-wave infarction (502+/-436 IU/l vs 1878+/-1265 IU/l, P<0.001). In spite of this, the extent of MIBG defects was similar in patients with a non-Q-wave and patients with a Q-wave infarction (21%+/-18% vs 23%+/-12%, respectively). In addition, the size of MIBG defect correlated with the infarct size (maximal creatine kinase activity) (r=0.52, P<0.05) after a Q-wave infarction but not after a non-Q-wave infarction. In conclusion, despite a smaller infarct size in non-Q-wave infarct patients, the extent of cardiac adrenergic denervation was similar in patients with a non-Q-wave and patients with a Q-wave infarction. In addition, the extent of cardiac adrenergic denervation was related to the infarct size in patients with a Q-wave infarction but not in patients with a non-Q-wave infarction.

3-Iodobenzylguanidine↗

PubMed2000

Multiple founder effects and geographical clustering of BRCA1 and BRCA2 families in Finland.

In the Finnish breast and ovarian cancer families six BRCA1 and five BRCA2 mutations have been found recurrently. Some of these recurrent mutations have also been seen elsewhere in the world, while others are exclusively of Finnish origin. A haplotype analysis of 26 Finnish families carrying a BRCA1 mutation and 20 families with a BRCA2 mutation indicated that the carriers of each recurrent mutation have common ancestors. The common ancestors were estimated to trace back to 7-36 generations (150-800 years). The time estimates and the geographical clustering of these founder mutations in Finland are in concordance with the population history of this country. Analysis of the cancer phenotypes showed differential ovarian cancer expression in families carrying mutations in the 5' and 3' ends of the BRCA1 gene, and earlier age of ovarian cancer onset in families with BRCA1 mutations compared with families with BRCA2 mutations. The identification of prominent and regional BRCA1 and BRCA2 founder mutations in Finland will have significant impact on diagnostics in Finnish breast and ovarian cancer families. An isolated population with known history and multiple local founder effects in multigenic disease may offer distinct advantages also for mapping novel predisposing genes.

Adult↗

PubMed2000

Cardiac adrenergic innervation within the first 3 months after acute myocardial infarction.

It is widely accepted that myocardial infarction results in adrenergic denervation of the infarcted and peri-infarcted myocardium. On the contrary, the concept of re-innervation of adrenergic nerve fibres is less well established. Although there is evidence of partial re-innervation occuring several months after myocardial infarction, the extent and time scale of re-innervation are only poorly known. In this study we investigated changes in cardiac adrenergic innervation and myocardial perfusion during the early convalescence period (the first 3 months) after an acute myocardial infarction. Single-photon emission computed tomographic imaging was conducted in 15 men 1 week and 3 months after an acute myocardial infarction with I123-metaiodobentzylguanidine (MIBG) and Tc99m-sestamibi (MIBI) to determine the extent of adrenergic denervation and impaired perfusion, respectively. A MIBG and MIBI defect was determined as regional uptake </=30% of maximal myocardial activity. The size of the MIBG defect calculated as a percentage of left ventricular mass remained unchanged between 1 week and 3 months after myocardial infarction (31.1 +/- 17.3% vs. 30. 5 +/- 16.8%, respectively). Accordingly, MIBG activity of the infarct and peri-infarct zones (expressed as a percentage of MIBG activity of the myocardium with normal perfusion) showed no significant change (23.7 +/- 10.0% vs. 25.3 +/- 11.0% and 39.0 +/- 11.3% vs. 40.8 +/- 12.8%, respectively) during the follow-up. On the other hand, the size of MIBI defect decreased significantly during the follow-up (14.2 +/- 11.5% vs. 11.4 +/- 9.7%, P<0.05, respectively) indicating improved myocardial perfusion. The results demonstrate that cardiac adrenergic re-innervation is a slow process; despite a significant increase in myocardial perfusion we found no evidence of adrenergic re-innervation during the first 3 months after acute myocardial infarction.

3-Iodobenzylguanidine↗

PubMed2000

Conscious sedation and cardiorespiratory safety during colonoscopy.

BACKGROUND: Cardiorespiratory events during colonoscopy are common. The effect of sedative premedication on cardiorespiratory parameters during colonoscopy has not been studied in controlled, prospective trials. METHODS: One hundred eighty patients undergoing colonoscopy were divided into 3 groups: (1) sedation with intravenous midazolam (midazolam group); (2) sedation with intravenous saline (placebo group); and (3) no intravenous cannula (control group). Arterial oxygen saturation (SaO(2)), systolic and diastolic blood pressure and continuous electrocardiogram were recorded prior to, during and after the endoscopic procedure. RESULTS: Midazolam produced lower SaO(2) values during colonoscopy compared with placebo or control groups (p < 0.001, repeated measures analysis of variance). Systolic and diastolic blood pressure during colonoscopy were lower in the midazolam group than in the placebo group (p < 0.01 and p < 0.05, respectively), but no difference was found between the midazolam and the control groups. Hypotension (systolic blood pressure less than 100 mm Hg) occurred more frequently in the midazolam group (19%) than in the placebo (3%; p < 0.01) or control groups (7%; p < 0.05). ST-segment depression developed in 7% of patients during the recording with no difference between the groups. In 75% of cases ST-depression appeared prior to the endoscopic procedure. CONCLUSIONS: Premedication with midazolam induced a statistically significant decrease in arterial oxygen saturation and increased the risk for hypotension. However, colonoscopy proved to be a safe procedure both with and without sedation.

Adult↗

PubMed2000

Effect of conscious sedation on cardiac autonomic regulation during colonoscopy.

BACKGROUND: Colonoscopy is associated with cardiovascular events including hypotension, hypertension, and myocardial ischemia. The pathogenetic mechanisms of these cardiovascular events are unknown, but there is evidence that the autonomic nervous system may play a role. Conscious sedation is often used to relieve the inconvenience caused by the procedure. In this study, we evaluated the effects of sedation on cardiac autonomic regulation during colonoscopy. METHODS: One hundred and eighty patients undergoing elective colonoscopy were prospectively randomized into three groups: (i) sedation with intravenous midazolam (midazolam group); (ii) sedation with intravenous saline (placebo group); and (iii) no intravenous cannula (control group). Continuous electrocardiogram was recorded prior to, during, and after the colonoscopic procedure. Heart rate variability (HRV) was assessed by means of the power spectral analysis; the powers of low-frequency (LF 0.04-0.15 Hz) and high-frequency (HF 0.15-0.40 Hz) components were calculated. RESULTS: Intubation of the colonoscope increased the LF component of HRV and decreased HF power in all study groups compared to baseline recording. Furthermore, compared to baseline, the LF/HF ratio--a marker of cardiac sympathetic regulation--increased during intubation in the midazolam (P < 0.001) and placebo (P < 0.05) groups, with no change in the control group. During intubation the midazolam group presented with higher LF and lower HF power than placebo (P < 0.001) and control groups (P < 0.01). Accordingly, the LF/HF ratio was higher in the midazolam group than in the placebo (P < 0.05) or control groups (P < 0.05). CONCLUSIONS: Midazolam potentiates the dominance of the sympathetic nervous system induced by colonoscopy. Therefore, conscious sedation with midazolam may contribute to the occurrence of cardiovascular events during colonoscopy.

Colonoscopy↗

PubMed2000

Effects of dobutamine on splanchnic tissue perfusion during partial superior mesenteric artery occlusion.

OBJECTIVE: To evaluate the effects of dobutamine and fluid treatment on splanchnic hemodynamics and tissue oxygenation during partial superior mesenteric artery occlusion. DESIGN: Prospective, open randomized, full-factorial design. SETTING: University research laboratory. SUBJECTS: Forty-eight female pigs. INTERVENTIONS: In 24 anesthetized pigs (ischemic group), superior mesenteric artery (SMA) blood flow was reduced to 30% from the baseline for 120 mins; 24 pigs (sham group) served as nonischemic controls. The animals were further assigned into four treatment arms. In the control arm, the animals were administered only basic fluid therapy. In the fluid therapy arm, pulmonary artery occlusion pressure was maintained at 10 mm Hg with fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arm, dobutamine at 10 microg/min/kg was administered and pulmonary artery occlusion pressure was maintained at 10 mm Hg with fluids. MEASUREMENTS AND MAIN RESULTS: Systemic and regional hemodynamics and oxygen transport, as well as jejunal intramucosal pH, intramucosal-arterial PCO2 gradient, and portal venous-arterial lactate gradient were measured. Ischemia did not modify the effects of fluids or dobutamine on systemic hemodynamics and oxygen transport. Dobutamine-treated animals had a higher cardiac index compared with control animals (218 +/- 22 vs. 135 +/- 13 mL/min/kg; p = .012), and the effect was enhanced when dobutamine was combined with fluid treatment (365 +/- 23 mL/ min/kg; p = .019). Fluid treatment alone did not influence cardiac index, whereas it increased SMA blood flow compared with control groups (15 +/- 2 vs. 12 +/- 2 mL/min/kg; p = .023). Dobutamine also decreased the proportion of SMA blood flow of cardiac output compared with control groups (6 +/- 1 vs. 9% +/- 1%; p = .024). Other treatments had no effect on SMA blood flow. Ischemia increased intramucosal-arterial Pco2 gradient to 54.8 +/- 10.7 torr (7.31 +/- 1.43 kPa) (p = .002 vs. sham control) and decreased intramucosal pH to 7.13 +/- 0.06 (p = .028 vs. sham control). In the ischemic animals, dobutamine without fluid therapy reduced intramucosal pH further to 7.00 +/- 0.09 (p = .023 vs. ischemic control) and increased portal venous-arterial lactate gradient (p = .033). CONCLUSIONS: Dobutamine alone worsened splanchnic tissue perfusion during partial superior mesenteric artery occlusion. As compared with fluid treatment alone, the combination of fluid and dobutamine therapy did not improve tissue perfusion.

Animals↗

PubMed1999

Similar effect of revascularization on technetium-99m( )sestamibi and 15-(p-iodophenyl)pentadecanoic acid uptake in myocardial infarction patients.

To study its usefulness as a tracer for assessment of the perfusion and viability of myocardium, 15-(p-iodophenyl)pentadecanoic acid (IPPA) was compared with technetium-99m sestamibi (MIBI). Dual-tracer single-photon emission tomography rest imaging was performed no more than 2 months before and 3 months after coronary artery bypass grafting in 28 patients with previous anterior (n=13) or inferior (n=15) infarction. The size of MIBI and IPPA defects decreased from 14%+/-12% and 13%+/-9% to 10%+/-11% and 9%+/-7%, respectively (P<0.001 for both). The MIBI uptake increased in the infarct zones from 35%+/-11% to 43%+/-8% (P<0.001), and in the peri-infarct zones from 50%+/-11% to 55%+/-10% (P<0.05). The IPPA uptake increased in the infarct zones from 37%+/-11% to 44%+/-13% (P<0.001), and in the peri-infarct zones from 51%+/-11% to 57%+/-12% (P<0.05). In nine patients with improved regional echocardiographic wall motion score after bypass surgery, the pre-operative uptake values of both MIBI and IPPA in the infarct and peri-infarct zones were on average slightly but not significantly higher than in 19 patients with no observed improvement in regional wall motion score. In patients with improved regional wall motion, the MIBI scans and the IPPA scans showed (non-significant) decreases in defect size and increases in infarct and peri-infarct zone uptake after bypass surgery. Similar (in some cases significant) changes were observed in the patients without improvement in wall motion. Thus IPPA and MIBI provided similar information about perfusion and viability in pre- and postoperative evaluation of patients with clinically evident myocardial infarction and with normal global ejection fraction. Regardless of the tracer used, the resolution capability of the dual-tracer method with a rest imaging protocol was not sufficient to differentiate viable from non-viable infarction defects in unselected individual patients with a normal ejection fraction.

Coronary Artery Bypass↗

PubMed1999

Is routinely given conscious sedation of benefit during colonoscopy?

BACKGROUND: Sedative drugs are generally given to patients undergoing colonoscopy. However, the benefit of routinely administered conscious sedation for colonoscopy has not been studied in adequately controlled trials. METHODS: We randomly assigned 180 patients scheduled for diagnostic colonoscopy into 3 groups: (1) sedation with intravenous midazolam (midazolam group); (2) sedation with intravenous saline (placebo group); and (3) no intravenous cannula (control group). The endoscopist assessed the procedure immediately after the examination. The patients completed a questionnaire before leaving the endoscopy unit. Another questionnaire was sent to the patients 2 weeks after the examination. Answers were mainly given on a 100 mm visual analog scale. RESULTS: Shortly after the procedure, the patients in the midazolam group rated the examination less difficult than those in the placebo group (30 vs. 40 mm; p < 0.05; visual analog scale, 0 to 100 mm: 0 = not at all, 100 = extremely). However, no significant difference was found between midazolam and control groups (30 vs. 36 mm, respectively). Otherwise, there were no differences between the three groups with respect to the patients' or endoscopists' assessments or the examination time. CONCLUSIONS: Routinely administered sedation does not markedly increase patient tolerance or make colonoscopy technically easier.

Adult↗

PubMed1999

QT dispersion and late potentials during doxorubicin therapy for non-Hodgkin's lymphoma.

OBJECTIVES: To investigate effects of doxorubicin therapy on cardiac electrophysiology, with special emphasis on QT dispersion and late potentials, in lymphoma patients. DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult non-Hodgkin's lymphoma patients who received doxorubicin to a cumulative dose of 400-500 mg m-2. MAIN OUTCOME MEASURES: Standard 12-lead electrocardiogram (ECG) and signal-averaged ECG (SAECG) recordings were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m-2. RESULTS: Heart rate-corrected QT interval (QTc) increased from 402 +/- 4 to 416 +/- 5 ms (P = 0.002) during the study period. QT dispersion (variability in QT interval duration amongst the different leads of the standard 12-lead ECG) increased from 24.1 +/- 2.5 to 35.0 +/- 2.8 ms (P = 0.041) and QTc dispersion increased from 26.5 +/- 2.5 to 39.0 +/- 3.5 ms (P = 0.039). Five patients (18%) developed QT dispersion exceeding 50 ms. In addition, two patients (7%) developed late potentials during doxorubicin therapy. The changes in QTc duration, QT dispersion and late potentials occurred independently of the impairment of left ventricular function. CONCLUSIONS: Prolongation of QTc, increased QT dispersion and development of late potentials are indicative of doxorubicin-induced abnormal ventricular depolarization and repolarization. QT dispersion and late potentials are both known to be associated with increased risk of serious ventricular dysrhythmias and sudden death in various cardiac diseases. Thus, follow-up of these parameters might also be useful in assessing the risk of late cardiovascular events in cancer patients treated with anthracyclines.

Adult↗

PubMed1999

Natriuretic peptides as markers of cardiotoxicity during doxorubicin treatment for non-Hodgkin's lymphoma.

Thirty adult patients with non-Hodgkin's lymphoma who were planned to receive up to 8-10 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) to a cumulative doxorubicin dose of 400-500 mg/m2 were studied to evaluate the value of serial plasma atrial natriuretic peptide (ANP), N-terminal pro-ANP (NT-proANP) and brain natriuretic peptide (BNP) measurements in the early detection of doxorubicin-induced left ventricular dysfunction. Plasma levels of natriuretic peptides were measured before every treatment course and 4 wk after the last one. Cardiac function was monitored with serial radionuclide ventriculography. Twenty-eight patients were evaluable for cardiotoxicity. Clinical heart failure developed in 2 patients (7%). Left ventricular ejection fraction (LVEF) decreased from 58.0+/-1.3% to 49.6+/-1.7% (p <0.001). Plasma levels of ANP increased from 16.4+/-1.3 pmol/l to 22.7+/-2.4 pmol/l (p= 0.002), NT-proANP from 288+/-22 to 380+/-42 pmol/l (p = 0.019) and BNP from 3.3+/-0.4 to 8.5+/-2.0 pmol/l (p = 0.020). There was a significant correlation between the increase in plasma ANP and the decrease in LVEF (r = -0.447, p = 0.029), and a trend towards significance between the increase in NT-proANP and the decrease in LVEF (r=-0.390, p=0.059). The decrease in LVEF started very early and could already be seen after the cumulative doxorubicin dose of 200 mg/m2, whereas the increase in plasma natriuretic peptides was not evident until the cumulative doxorubicin dose of 400 mg/m2. Our results show that neuroendocrine activation - increased concentrations of plasma natriuretic peptides - occurs when left ventricular function has reduced substantially and its compensatory capacity has been exceeded resulting in atrial and ventricular overload. Thus, serial natriuretic peptide measurements cannot be used in predicting the impairment of left ventricular function. On the other hand, our study suggests that natriuretic peptides are useful in the detection of subclinical left ventricular dysfunction in patients receiving doxorubicin therapy.

Adult↗

PubMed1999

Sympathovagal balance is major determinant of short-term blood pressure variability in healthy subjects.

Short-term blood pressure variability (BPV) has been suggested to provide important information about cardiovascular regulation. However, the background of BPV, its determinants, and physiological correlates have remained obscure. The aim of this study was to characterize physiological correlates of BPV and to investigate associations between BPV and neural and hormonal regulatory systems at rest in healthy subjects. We studied 117 healthy, normal-weight, nonsmoking male and female subjects aged 23-77 yr. Spectral analysis of BPV and heart rate variability (HRV) was performed from 5-min blood pressure (Finapres) and electrocardiogram recordings during controlled breathing. Baroreflex sensitivity (BRS) was measured using the phenylephrine method. In addition, plasma concentrations of norepinephrine, epinephrine, and arginine vasopressin and plasma renin activity were measured. We found that the ratio between the low- and high-frequency components of HRV, an index of cardiac sympathovagal balance, correlated positively with total power and very low- and low-frequency components of systolic and diastolic BPV and inversely with high-frequency components of systolic and diastolic BPV. BRS, predominantly a measure of cardiac vagal regulation, correlated inversely with BPV. Furthermore, age, gender, body mass index, and systolic blood pressure contributed to BPV. Vasoactive hormones were not significant correlates of BPV. We conclude that sympathovagal balance of cardiovascular regulation is the major determinant of BPV. Other factors associated with BPV are age, gender, body mass index, blood pressure, and BRS.

Adult↗

PubMed1998

Adenovirus-mediated gene transfer to lower limb artery of patients with chronic critical leg ischemia.

Arterial gene transfer offers a promising new approach for the treatment of vascular disorders. However, no data are available about the gene transfer efficiency in human arteries in vivo. The aim of this study was to evaluate the safety and feasibility of catheter-mediated adenoviral gene transfer in human peripheral arteries. Ten patients (8 females, 2 males, mean age 80 +/- 8 years) suffering from chronic critical leg ischemia with a prior decision for amputation were recruited in the study. Gene transfer was performed in eight patients in conjunction with a conventional percutaneous transluminal angioplasty, using a perfusion coil balloon catheter. Two patients served as controls. Increasing concentrations of replication-deficient adenoviruses (titers from 1 x 10(8) to 4 x 10(10) PFU) containing a nuclear-targeted beta-galactosidase marker gene were administered into the arteries over 10 min via the catheter. Amputations were performed 20 to 51 hr after the procedures and gene transfer efficiency was evaluated in the transduced arteries using X-Gal staining for beta-galactosidase activity. Beta-galactosidase gene transfer was well tolerated and no adverse tissue responses or systemic complications were observed in any of the patients. Gene transfer was successful in six of the eight patients. Gene transfer efficiency varied between 0.04 and 5.0% of all arterial cells. Transgene expression was detected in smooth muscle cells, endothelial cells, and macrophages and in tunica adventitia. However, transgene activity was not evenly distributed in the arterial wall and no transgene activity was found beneath advanced atherosclerotic lesions. The safety and feasibility of in vivo gene transfer by adenoviral vectors to human peripheral arteries were established. Although improvements are still required in gene transfer efficiency, these findings suggest that adenoviruses can be used to deliver therapeutically active genes into human arteries.

Adenoviridae↗

PubMed1998

Significance of coronary artery bypass grafting-associated conduction defects.

The incidence of permanent atrioventricular conduction defects (CDs) caused by coronary artery bypass grafting (CABG) varies from 5% to 43% if cold crystalloid or blood cardioplegia is used for myocardial preservation. However, the long-term effects of CDs on clinical outcome are not well known. In this study we compared the outcome of 52 patients with permanent CABG-associated CDs (CD+) to 47 patients without CDs (CD-) after a 3-year follow-up. Recovery of CDs was found in 2 patients during the follow-up. There were no significant differences between groups in late mortality, cardiac or neurologic events, or capability to work. Although exercise capacity was similar, the exercise-limiting symptom more often was chest pain or dyspnea in the CD+ group than in the CD- group (p = 0.001). Left ventricular ejection fractions at rest and at 50-W workload level were lower in the CD+ group (p = 0.03 to 0.05). In addition, CD+ patients with left bundle branch block or cardiac pacemaker had significantly lower ejection fraction at maximal workload level than patients without CDs (p = 0.03). No significant differences were observed between the groups in the potential risk for ventricular arrhythmias according to signal-averaged electrocardiograms. In conclusion, the clinical outcome of patients with CDs after CABG operations is almost comparable to those without CDs during a 3-year follow-up. However, patients with CDs have lower left ventricular systolic function and more often have chest pain or dyspnea as the exercise-limiting symptom than patients without CDs.

Aged↗