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Biomedical subjects

G Sani

Publications and source records attributed to G Sani.

At least 19 recordsLinked to original sources
PubMed2005

Early and late outcome of skeletonised bilateral internal mammary arteries anastomosed to the left coronary system.

OBJECTIVES: To investigate in a retrospective study the technical aspects of using the in situ bilateral internal mammary arteries (IMAs), with the right IMA (RIMA) used for revascularisation of the circumflex system, and to evaluate early and late outcome. MATERIALS AND METHODS: Between January 1997 and July 2003, 552 consecutive patients underwent grafting of the circumflex artery system with an in situ skeletonised RIMA routed through the transverse sinus (eventually retrocaval). Mean (SD) age was 63.8 (11) years. 331 (60%) patients underwent total arterial myocardial revascularisation. Mean follow up was 26 (9) months. RESULTS: The success rate of skeletonised RIMA grafting to the circumflex branch was 100%. There were 19 (3.4%) in-hospital deaths. Perioperative myocardial infarction occurred in 12 (2.2%) patients. In 155 patients undergoing postoperative angiography, two had an occluded RIMA and a string-like phenomenon was seen in three RIMA and one left IMA (LIMA). Three RIMA and three LIMA had stenotic lesions. The patency rates of RIMA and LIMA were 94% and 97.4%, respectively. Strong predictors of non-functional IMA grafts were a recipient coronary artery diameter of < 1.5 mm (p = 0.022), < 60% stenosis of the recipient coronary artery (p = 0.015), diffuse stenotic lesions of the recipient coronary artery (p = 0.018), and a small IMA calibre (p = 0.0001). Cumulative actuarial survival at three years was 96.4% and event-free cumulative survival was 93.8%. CONCLUSIONS: Use of the bilateral IMAs offers the possibility of constructing various configurations, making total arterial myocardial revascularisation possible with a minimum number of arterial conduits. Use of the skeletonised RIMA through the transverse sinus and eventually retrocavally can reach most branches of the circumflex system and is associated with an excellent patency rate. Patients who received bilateral IMA grafts for left coronary system revascularisation had improved early and late outcomes and decreased risk of death, reoperation, and angioplasty.

Adult↗
PubMed2003

Duration and stability of the rapid-cycling course: a long-term personal follow-up of 109 patients.

BACKGROUND: Recognition by the DSM-IV of rapid cyclicity as a course specifier has raised the question of the stability and long-term outcome of rapid-cycling (RC) patients. Data on this topic is sparse and often inconsistent. To our knowledge, these are the first personally followed patients over the long term, dealing directly with the issue of the duration of the RC course. METHODS: We examined the evolution of the course of 109 RC patients (68 women and 41 men) followed for a minimum of 2 years and up to 36 years, beginning with the index episode when the RC course was diagnosed by the authors (A.K., G.P.M., P.G., L.P., D.R.). Patients were included in the study if they met criteria for RC as defined by>or=4 affective episodes per year (Dunner and Fieve, 1974). The follow-up period varied from 2-5 years for 25 patients, 6-10 years for 24 patients, 11-15 years for 24 patients, 16-20 years for 19 patients, 21-25 years for 13 patients, 30-36 years for four patients. RESULTS: In 13 patients (12%), RC emerged spontaneously and in 96 patients (88%), it was associated with antidepressant and other treatments. In 19 women (28% of all women) RC course started in perimenopausal age (45-54 years). The mean duration of RC during the follow-up period was 7.86 years (range 1-32) and its total duration (including RC course prior to the follow-up period) was 11 years (range 1-40). The total duration of the affective disorder, from the first episode to the end of the follow-up, was 21.78 years (range 1-70). At the end of the follow-up, 36 patients (33%) had complete remission for at least the past year, 44 (40%) stayed rapid cycling with severe episodes (six of this group committed suicide), while 15 (14%) were rapid cycling but with attenuated episodes. The other 14 patients (13%) became long cyclers, eight with severe episodes and six with milder ones. The main distinguishing features between those who remitted from and those who persisted in the RC course were: (1). the initial cycle pattern: patients with Depression-Hypomania(mania)-Free interval cycles (53 patients) had a worse outcome: 26.4% remitted and 52.8% persisted in the RC course through to the end of the follow up period. The Mania/Hypomania-Depression-Free interval cycles (22 patients) had a significantly better outcome, with 50% remitted and 27.2% persisting RC; and (2). the occurrence of the switch process from depression to hypomania/mania and the occurrence of agitated depressions made the prognosis worse. Continuous treatment was more effective against mania/hypomania than against depression, yet in all persisting RC cases the mania/hypomania remitted only partially. LIMITATIONS: These data derive from clinics known for their expertise in mood disorders, and they may have attracted and retained patients with a more severe course. Treatment was uncontrolled and consisted more of lithium than divalproex, lamotrigene and olanzapine, recently shown to be beneficial in subgroups of patients with rapid-cycling. CONCLUSIONS: Our findings suggest that rapid cyclicity, spontaneous or induced, once established, becomes for many years a stable rhythm in a substantial proportion of patients, linked to endogenous and environmental factors. The suggestion is made to consider as rapid-cyclers, at least for research purposes, those patients who have had a rapid cycling course for at least 2 years, borrowing the duration criterion currently employed for other chronic disorders such as Dysthymia and Cyclothymia. That our patients had poorer prognosis than some other cohorts in the literature is probably due to the shorter duration of "rapid-cycling" at entry in the latter cohorts. A true understanding of the nature of rapid-cycling will require a rigorous definition of not only duration, but also pole-switching and course patterns at entry into study.

Adult↗
PubMed2002

Emergency management of spontaneous coronary artery dissection.

Six cases of spontaneous coronary arteries dissection are reported. In one patient, triple vessel spontaneous coronary artery dissection was identified. Another patient presented spontaneous left main coronary artery dissection. In one case we found the spontaneous dissection of the left anterior descending artery associated with distal aortic arch dissection. These conditions are very rare and may present a surgical dilemma. Causative factors and underlying pathology are clarified. Prompt diagnosis and surgical intervention is safe and effective. Early recognition of left main coronary artery dissection or three-vessel dissection is essential because urgent coronary artery bypass grafting may be life saving.

Adult↗
PubMed2001

Clinically relevant cognitive impairment after cardiac surgery: a 6-month follow-up study.

BACKGROUND AND PURPOSE: The majority of studies on neuropsychological complications after cardiac surgery used the raw variation of selective tests scores to define the occurrence of cognitive decline. We prospectively estimated the frequency of cognitive impairment after cardiac surgery, with a particular emphasis on persistent and clinically relevant cognitive decline. Possible baseline and operative predictors were also evaluated. METHODS: An extensive neuropsychological battery was administered to 110 patients (mean age 64.1+/-9.4 years; 70.9% males) undergoing cardiac surgery before and 6 months after the operation. After evaluating the variations in the cognitive performances, two independent neuropsychologists ranked the patients as unchanged-improved, mildly-moderately deteriorated, or severely deteriorated, using a global and functionally oriented judgement. The degree of the impairment was determined in relation to its impact on everyday life activities. RESULTS: Ten patients (9.1%) were ranked as severely deteriorated, 22 (20%) as mildly-moderately deteriorated, and 78 (70.9%) as unchanged-improved. Cognitively impaired patients were older (p=0.031), more often females (p=0.005), with a low education level (p=0.013). At multivariate analysis, female gender (odds ratio (OR) 6.14, 95% confidence interval (95% CI) 2.16-17.50), baseline use of beta-blockers (OR 4.55, 95% CI 1.30-15.92), and PaO2 at arrival in intensive care unit (OR for 1 mm Hg increment 1.012, 95% CI 1.004-1.020) were significant predictors of cognitive impairment of any degree. Positive predictors of severe cognitive impairment were history of hypertension (OR 5.33, 95% CI 1.03-27.64) and PaO2 at arrival intensive care unit (OR for 1 mm Hg increment 1.020, 95% CI 1.006-1.035), while education was protective (OR per year of increment 0.53, 95% CI 0.31-0.90). CONCLUSIONS: A considerable proportion of cardiac surgery patients may undergo clinically relevant cognitive impairment. The knowledge of variables influencing cognitive outcome is essential for the adoption of preventive measures.

Adult↗
PubMed2001

The properties of the pacemaker current I(F)in human ventricular myocytes are modulated by cardiac disease.

The pacemaker current I(f)is present in ventricular myocytes from the human failing heart where it may contribute to arrhythmogenesis. The role of cardiac disease in the modulation of I(f)expression is still uncertain. We studied the functional expression and properties of I(f)in human ventricular myocytes isolated from control donor hearts or from explanted failing hearts of patients with ischemic and dilated cardiomyopathy. In patch-clamped cells, I(f)was elicited by hyperpolarization. Membrane capacitance (C(m)) was significantly higher in dilated cardiomyopathy than in control or ischemic cardiomyopathy. I(f)was present in all ischemic and dilated cardiomyopathy tested cells and in 76% of control cells. In ischemic and dilated cardiomyopathy, I(f)amplitude measured at -120 mV was significantly greater than in control. However, I(f)density (i.e. current normalized to C(m)) was significantly higher in ischemic cardiomyopathy (2.0+/-0.2 pA/pF) than in dilated cardiomyopathy (1.2+/-0.1 pA/pF) or control (1.0+/-0.1 pA/pF). In diseased hearts, the activation curve was significantly shifted to more positive values compared to control. The slope of the fully-activated I-V relations was greater in ischemic cardiomyopathy than in dilated cardiomyopathy or control (P<0.05) while the intercept with the x -axis (V(rev)) was similar. In conclusion, I(f)is overexpressed in human ventricular myocytes from failing hearts; its functional expression seems related to the etiology of the disease, being higher in ischemic than in dilated cardiomyopathy, and not to the degree of cell hypertrophy.

Adult↗
PubMed2001

Beating heart myocardial revascularization on extracorporeal circulation in patients with end-stage coronary artery disease.

OBJECTIVES: To evaluate in a cohort of ESCAD patients (pts) the effects of on-pump/beating-heart versus conventional CABG in terms of early and mid-term survival and morbidity and LV function improvement. METHODS: Between January 1993 and December 2000, 78 (Group I) ESCAD pts underwent on-pump/beating-heart surgery. Mean age in Group I was 66.2+/-6 (58-79), NYHA and CCS class were 3.2+/-0.6 and 3.3+/-0.4 respectively, Myocardial viability index 0.69+/-0.1 (%), LVEF (%) 24.8+/-4, LVEDP (mmHg) 28.1+/-5.8 and LVEDD(mm) 69.5+/-6. Group II consisted in 78 ESCAD patients undergoing conventional CABG selected in a randomized fashion from an age, sex, and LVEF corrected group of patients. Mean age in Group II was 65.7+/-5 (57-78), NYHA 3.1+/-0.7, CCS 3.4+/-0.8, LVEF(%) 25+/-5, LVEDP(mmHg) 27.9+/-4.4 and LVEDD(mm) 69.2+/-7.2. RESULTS: Postoperatively, 5(7.7%) patients died in Group I versus 7(11.5%) patients in Group II (P>0.1). CPB time resulted to be in Group II patients (P=0.001) and the mean distal anastomoses per patient was similar between groups (P=Ns). Perioperative AMI (P=0.039), LCOS (P=0.002), necessity for ultrafiltration (P=0.018) and bleeding>1000 ml (P=0.029) were significantly higher in Group II. None of the Group I patients underwent surgical revision for bleeding versus 8(10.3%) patients in Group II (P=0.011). At 6 months after surgery, the LV function improved significantly in Group I patients, demonstrated by an increased LVEF=27.2+/-4(%)(P=0.001), lower LVEDP=26.4+/-3(mmHg)(P=0.029) and LVEDD=67+/-4(mm) (P=0.004) instead of a lower LVEDD=66.8+/-6(mm)(P=0.032) versus the preoperative data in Group II. The actuarial survival at 1, 3 and 5 yr were 90, 82 and 71% in Group I and 89, 83 and 74% in Group II (P=Ns). CONCLUSION: In ESCAD patients who may poorly tolerate cardioplegic arrest, on-pump/beating-heart CABG may be an acceptable alternative associated with lower postoperative mortality and morbidity. Such a technique offers a better myocardial and renal protection associated with lower postoperative complications due to intraoperative hypoperfusion.

Aged↗
PubMed2001

Respiratory dysfunction after coronary artery bypass grafting employing bilateral internal mammary arteries: the influence of intact pleura.

OBJECTIVE: To evaluate the role of intact pleurae regarding the postoperative respiratory functional status in patients undergoing coronary revascularization employing both internal mammary arteries (IMAs), according to the pedunculated or skeletonized technique (SKT) with opened or intact pleurae. MATERIALS AND METHODS: Using both IMAs, 299 patients underwent elective coronary revascularization. They were randomized and divided into group I (n=82, undergoing IMA harvesting according to the SKT without opening the pleurae); group II (n=186, undergoing IMA harvesting according the pedunculated technique with open pleurae); and group III (n=31, undergoing IMA harvesting according the SKT with incidentally opened pleurae). There were no differences regarding the preoperative patient characteristics and the anaesthetic and surgical management. RESULTS: There were two deaths in group I versus seven in group II and one in group III (P=ns). The number of total arterial myocardial revascularization and arterial composite grafts was significantly higher in groups I and III than in group II, (P<0.001 and P<0.005, respectively). The incidence of postoperative complications was similar between groups. Blood loss of >1000 ml was significantly higher in group II than group I (P<0.028); but the incidence of re-thoracotomy and blood transfusion was similar between groups. The mechanical ventilation time was significantly higher in groups II and III versus group I (P<0.018 and P<0.02, respectively). The incidence of prolonged ventilation (>24 h), pleural effusion, thoracocentesis and atelectasis, resulted in being significantly higher in group II than group I. The incidence of thoracocentesis was significantly higher in group III than group I. The pain score and analgesic requirements at 1-12 h after awakening were significantly higher in groups II and III versus group I, becoming similar after the chest tubes were removed. PaO(2) was significantly higher, and PaCO(2) and FiO(2) were significantly lower in group I than groups II and III at 1 and 4 h before extubation and at 1 and 4 h after extubation. PaO(2) and PaCO(2) became similar between groups at the 5th postoperative day. CONCLUSIONS: According to our results, we may conclude that pleural integrity has beneficial effects on the respiratory functional status after coronary revascularization using both IMAs. A meticulous and more careful IMA harvesting approach significantly reduces the postoperative morbidity regarding the pulmonary functional status, and as a consequence, reduces the hospital costs.

Blood Loss, Surgical↗
PubMed2001

Urgent surgical revascularization of unstable angina. Influence of double mammary arteries.

OBJECTIVE: Aim of this study was to evaluate retrospectively: (1) the outcome in patients with unstable angina (UA) refractory to the medical therapy undergoing urgent-emergent CABG; (2) the influence of both IMAs employment. PATIENTS AND METHODS: Between January 1995 and July 2000, 576 (28.5%) consecutive patients with UA underwent CABG procedure. 182 (31.6%, Group I) patients, presenting unstable hemodynamic or angina pectoris refractory to the maximal medical therapy, underwent urgent/emergent CABG. 397 (68.4%, Group II) patients, after the maximal medical therapy did not present angina's episodes or ECG alterations and underwent elective CABG procedure. Preoperative data were similar in the two groups. Both IMAs were used in 68 (37.4%) patients of I and 152 (38%) of II (P>0.05) to left side revascularization. RESULTS: CAD extension was greater in Group I: 45 (24.7%) patients presented ischemia in >1 area vs 53 (13.5%) in II (P<0.001). Incidence of anteroseptal ischemia resulted significantly higher in I (P=0.017); left main coronary artery stenosis was present in 68 (37%) patients in I vs 108 (27%) in II (P=0.01). LV function resulted significantly depressed in I, demonstrated by a significantly lower LVEF (P<0.001), higher NYHA class (P<0.001) and preoperative incidence of IABP (P<0.001). Intraoperative data analysis did not reveal any difference between groups. Hospital mortality was 13 (7%) and 21 (5.3%) patients in I and II respectively (P=ns). Multivariate analysis of all preoperative and intraoperative variables revealed the age >65 years (P=0.01), congestive heart failure (P<0.001), LVEF<35% (P=0.03), >1 ischemic area (P=0.02) as strong predictors for poor overall survival, and LIMA (P=0.006) and both IMAs (P=0.001) as strong predictors for good overall survival. Actuarial survival at 1, 3 and 5 years resulted to be 98.5, 96.5 and 90% in I and 99, 96 and 92% in II (P=ns). CONCLUSION: CABG has been associated with acceptable outcome in patients with UA which should be applied soonest possible in patients refractory to medical treatment. Total coronary revascularization and employment of both IMAs for left myocardial side are associated with low operative risk and incidence of complications, permit to have acceptable short and long-term outcome in this pool of patients.

Aged↗
PubMed2001

Ischemic mitral valve regurgitation grade II-III: correction in patients with impaired left ventricular function undergoing simultaneous coronary revascularization.

BACKGROUND AND AIM OF THE STUDY: Mitral valve regurgitation (MVR), occurring as a result of myocardial ischemia and global left ventricular (LV) dysfunction, is predictive of poor outcome. The study aim was to assess the feasibility of mitral valve surgery concomitant with coronary artery bypass grafting (CABG) in patients with ischemic MVR grade II-III and impaired LV function. METHODS: Between January 1996 and July 2000, 99 patients with grade II and III ischemic MVR and LV ejection fraction (LVEF) 17-30% underwent either combined mitral valve surgery and CABG (group I, n = 49) or isolated CABG (group II, n = 50). LVEF (%), LV end-diastolic diameter (LVEDD; mm), LV end-diastolic pressure (LVEDP; mmHg), LV end-systolic diameter (LVESD; mm) respectively were 27.5+/-5, 67.7+/-7, 27.7+/-4 and 51.4+/-7 in group I versus 27.8+/-4, 67.5+/-6, 27.5+/-5 and 51.2+/-6 in group II. In group I, mitral valve repair was performed in 43 patients (88%) and replacement in six (12%). RESULTS: Preoperative data analysis showed no difference between groups. Five patients (10%) died in group I, compared with six (12%) in group II (p = NS). Within six months of surgery, LV function and geometry improved significantly in group I versus group II (LVEF, p <0.001; LVEDD, p = 0.002; LVESD, p = 0.003, LVEDP, p <0.001); only mild improvements were seen in group II. The regurgitation fraction decreased significantly in group I patients after surgery (p <0.001). Cardiac index increased significantly in groups I and II (p <0.001 and p = 0.03, respectively). In group I at follow up, four of six patients undergoing mitral valve replacement died, compared with five of 43 patients (11.5%) undergoing mitral valve repair (p = 0.007). At three years, the overall survival in group II was significantly lower than in group I (p <0.009). CONCLUSION: Both MV repair and replacement preserving subvalvular apparatus in patients with impaired LV function offered acceptable outcome in terms of morbidity and survival. Surgical correction of grade II-III MVR in patients with impaired LV function should be taken into consideration as it provides better survival and improves LV function.

Actuarial Analysis↗
PubMed2000

Selective upregulation of cardiac endothelin system in patients with ischemic but not idiopathic dilated cardiomyopathy: endothelin-1 system in the human failing heart.

Only scarce information is available on the activity and modifications of the cardiac endothelin (ET)-1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro-ET-1 (ppET-1), ET-converting enzyme-1, and ET(A) and ET(B) receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription-polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ET(A) and ET(B) receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P<0.001 for all). ppET-1 and ET-converting enzyme-1 mRNAs were expressed on myocytes and endothelial and interstitial cells in ICM, whereas in DCM and nonfailing hearts they were mainly expressed on nonmyocyte cells. In both ICM and DCM, the ET(A) mRNA signal was expressed on both myocytes and nonmyocyte cells, whereas ET(B) mRNA was almost exclusively localized on nonmyocyte cells. ET(A)- and ET(B)-specific receptor binding was increased on both myocytes and cardiac membranes, showing a positive correlation with left ventricular ejection fraction in ICM (r=0.78 and 0.70) but not in DCM patients. The present results show that human ventricular myocytes express all of the components of the ET-1 system, which is selectively upregulated in ICM patients and appears to be functionally important in the maintenance of cardiac function.

Adult↗
PubMed2000

Capillary electrophoresis in the evaluation of ischemic injury: simultaneous determination of purine compounds and glutathione.

An understanding of tissue energy metabolism and antioxidant status is of major interest in the field of organ preservation for transplantation. Nucleotide and glutathione are indicators of cell damage occurring during ischemia and reperfusion. A high performance capillary electrophoresis (HPCE) method with UV detection (185 nm) for the simultaneous analysis of intracellular free ribonucleotides, nucleosides, bases and glutathione (oxidized and reduced form) in myocardial tissues is described. The method does not involve thiol derivatization. The separations were carried out in an uncoated fused-silica capillary, 60 cm long, 52.5 cm to detector, 75 microm ID, with 20 mM Na-borate buffer, pH 10.00, at 20 kV voltage and reading at 185 nm. Injection was hydrostatic for 12 s and total analysis time was 20 min. The technique enables optimum separation of all the compounds examined and has a resolution similar to that of HPLC analysis, with the advantage of fast simultaneous measurement of cell nucleotide metabolism and redox state, not possible with HPLC.

Adolescent↗
PubMed2000

Prognostic value of baroreflex sensitivity assessed by phase IV of Valsalva manoeuvre in patients with mild-to-moderate heart failure.

BACKGROUND: In patients with heart failure, impairment of baroreflex function occurs early and contributes to sympathetic activation, however, at present its prognostic role has not been definitively established. AIMS: To evaluate the prognostic significance of baroceptor impairment in patients with different degrees of heart failure. METHODS: We enrolled 52 consecutive patients with heart failure, referred to our institution for functional evaluation. Twenty-eight suffered from ischemic cardiomyopathy and 26 from dilated cardiomyopathy. Thirteen patients were in NYHA class I, 20 in NYHA class II and 19 in class III. All patients underwent baroreflex assessment by phase IV Valsalva manoeuvre using Finapres finger monitoring of arterial blood pressure, echocardiography [with evaluation of left ventricular ejection fraction (LVEF), fractional shortening (LVFS), left ventricular end diastolic diameter (LVEDD) and mean pulmonary artery pressure] and functional evaluation by cardiopulmonary exercise test and 6-min walk corridor test within 2 days of hospital admission. RESULTS: Mean duration of follow-up was 26 months (range 6-35 months). At baseline, evaluation in 13 patients BRS was normal (>5 ms/mmHg), in 17 moderately impaired (1.5-5 ms/mmHg) and in 22 severely depressed (<1.5 ms/mmHg). Baroreflex function was relatively preserved in patients in NYHA class I (5.1+/-2.5) in comparison to patients in NYHA class II and III (2.1+/-2.3 and 2.08+/-1.9 ms/mmHg, respectively). Of the 52 patients who entered the study at the end of follow-up 15 died of cardiac cause and 5 underwent heart transplantation. Survival free from heart transplantation was 62% in patients with normal baroreflex function, 62% in patients with moderate impairment of baroreflex and 66% in patients with major derangement. NYHA class, LVEF, LVFS and LVEDD were significantly associated with event free survival while baroreflex function was not. CONCLUSIONS: Our results suggest that evaluation of BRS impairment by phase IV Valsalva manoeuvre has limited prognostic value in patients with heart failure.

Adult↗
PubMed2000

Electrophysiologic effects of lercanidipine on repolarizing potassium currents.

Blockade of cardiac repolarizing potassium channels by drugs may result in QT-interval prolongation, eventually degenerating into "torsades de pointes," a life-threatening arrhythmia. Lercanidipine (LER) is a recently introduced lipophilic calcium antagonist with no cardiodepressant activity and long-lasting antihypertensive action. Its chemical structure is characterized by the presence of a diphenylpropylaminoalkyl group, which is present in some of the drugs that have been reported to cause QT-interval prolongation. Our previous data demonstrated that LER blocks L-type calcium channels without affecting sodium current; however, no data are available concerning its effects on cardiac potassium channels. Transient outward (I(to)), delayed rectifier (I(K)), background currents, and action potential (AP) profile were measured from patch-clamped ventricular myocytes isolated from rat, guinea pig, or human hearts using enzymatic dissociation procedures. LER did not affect I(K) (and I(Kr)) density and activation curve in guinea pig myocytes; the reversal potential of the background current (I(K1)) and its slope were not changed by the drug. Maximal diastolic potential (MDP) and duration of the AP measured at -60 mV (APD(-60)) were not significantly changed. I(to) density and activation curves measured in rat myocytes were similar in the absence and presence of 1 or 10 microM LER. Finally, the effect of LER was tested in human ventricular myocytes: superfusion with 1 microM LER did not affect MDP and APD(-60). I(to) density and the midpoint of activation and inactivation curves were similar in the absence and presence of LER. In conclusion, our data demonstrate that LER does not affect repolarizing potassium currents and action potential profile recorded from guinea pig, rat, and human ventricular myocytes. It is unlikely that LER could cause QT prolongation in vivo.

Action Potentials↗
PubMed1999

Endothelin receptors in adult human and swine isolated ventricular cardiomyocytes.

The present study aimed to investigate endothelin-1 (ET-1) receptors in human and swine cardiomyocytes with binding studies using ET(A) and ET(B) selective receptor antagonists (BMS-182874 and BQ-788, respectively). Cell distribution of mRNA expression for ET(A) and ET(B) subtypes was investigated by in situ hybridization using specific cDNA probes. The 1251-ET-1 binding, which reached equilibrium in about 120 min (Kobs = 0.051+/-0.003 min(-1)), was only partially displaceable by the addition of a large excess of ET-1 (about 15% with a half-life of 20 min). In equilibrium binding studies, 125I-ET-1 had a Kd of 0.43+/-0.08 nM and a maximum binding (Bmax) of 42.8+/-6.6 fmol/mg protein. ET(A) and ET(B) receptors are represented in human and swine cardiomyocytes with an 85:15 ratio as indicated by the biphasic pattern of competition of both BMS-182874 and BQ-788. In situ hybridization studies confirmed that myocytes mainly expressed mRNA for ET(A), whereas expression of mRNA for the ET(B) subtype was documented in non-myocyte cells. These results showed that ET-1 binds with high affinity and poor reversibility to specific receptors, in both human and swine isolated ventricular cardiomyocytes, without significant species differences.

Adult↗
PubMed1999

Cardiac growth factors in human hypertrophy. Relations with myocardial contractility and wall stress.

The aim of the present study was to investigate whether and which cardiac growth factors are involved in human hypertrophy, whether growth factor synthesis is influenced by overload type and/or by the adequacy of the hypertrophy, and the relationships between cardiac growth factor formation and ventricular function. Cardiac growth factor formation was assessed by measuring aorta-coronary sinus concentration gradient in patients with isolated aortic stenosis (n=26) or regurgitation (n=15) and controls (n=12). Gene expression and cellular localization was investigated in ventricular biopsies using reverse transcriptase-polymerase chain reaction and in situ hybridization. Cardiac hypertrophy with end-systolic wall stress <90 kdyne/cm2 was associated with a selective increased formation of insulin-like growth factor (IGF)-I in aortic regurgitation and of IGF-I and endothelin (ET)-1 in aortic stenosis. mRNA levels for IGF-I and preproET-1 were elevated and mainly expressed in cardiomyocytes. At stepwise analysis, IGF-I formation was correlated to the mean velocity of circumferential fiber shortening (r=0.86, P<0.001) and ET-1 formation to relative wall thickness (r=0.82, P<0. 001). When end-systolic wall stress was >90 kdyne/cm2, IGF-I and ET-1 synthesis by cardiomyocytes was no longer detectable, and only angiotensin (Ang) II was generated, regardless of the type of overload. The mRNA level for angiotensinogen was high, and the mRNA was exclusively expressed in the interstitial cells. Ang II formation was positively correlated to end-systolic stress (r=0.89, P<0.001) and end-diastolic stress (r=0.84, P<0.001). Multivariate stepwise analysis selected end-systolic stress as the most predictive variable and left ventricular end-diastolic pressure as the independent variable for Ang II formation (r=0.93, P<0.001). In conclusion, the present results indicate that the course of human left ventricular hypertrophy is characterized by the participation of different cardiac growth factors that are selectively related both to the type of hemodynamic overload and to ventricular function.

Aged↗
PubMed1999

Characterization of endothelin-1 receptor subtypes in isolated human cardiomyocytes.

On cardiac membranes and isolated cardiomyocytes from the human heart, cell-type distribution and functional activities of endothelin-1 (ET-1) receptor subtypes were investigated by using binding methods and messenger RNA (mRNA) in situ hybridization. The ET-receptor antagonist BMS-182874 selectively and competitively inhibits ET(A) receptors both on isolated myocytes and ventricular membranes with approximately 1,300 times greater affinity for ET(A) than ET(B) subtypes. The [125I]-ET-1 specific binding revealed 42.851+/-2,546 receptors/myocyte with a prevalent proportion of ET(A)-receptor subtypes on both myocytes (84+/-2%) and ventricular membranes (66+/-3%). In situ hybridization studies revealed that mRNA for ET(A) receptors was expressed on both myocytes and nonmyocyte cells, whereas mRNA for ET(B) receptors was almost exclusively expressed on fibroblasts and endothelial cells. Specific binding of [125I]-ET-1 to both myocytes and ventricular membranes in the presence of specific ET(A) (BMS-182874) and ET(B) (BQ-788)-receptor antagonists showed a displacement of [125I]-ET-1 by unlabeled ET-1, which were significantly faster from ET(B) than from ET(A). This suggests a clearance function of ventricular ET(B) receptors.

Antihypertensive Agents↗
PubMed1999

Siena's experience with pulmonary autograft operations: clinical and echocardiographic follow-up.

As there is no perfect aortic valve substitute, there is a need to find out which one is the best option to replace the diseased aortic valve. Any type of mechanical or biological stented device has a residual gradient and does not reproduce the extremely sophisticated normal aortic valve function. This may influence the short- and long-term outcome, especially in dilated and poorly contracting left ventricles which do not tolerate even a mild stenosis. Thus, the potentially ideal valve to replace the aortic valve is either an aortic valve (aortic homograft) or a pulmonary autograft in aortic position. These grafts are also less subject to endocarditis. It has been demonstrated that pulmonary autografts can grow when implanted in children and as they remain viable, they maintain their dynamic behavior and possibly the internal innervation of the cusps. Unfortunately, pulmonary autograft surgery is more demanding and lasts longer, which may increase the risk of the operation. In addition, the exact indications and applications of the operation, particularly in patients with poor left ventricles or additional lesions, have not been clearly defined. Here we report our experience with this technique in 11 patients with severe aortic valve disease, including those with poor left ventricle function and/or associated disease. We describe our short- and medium-term follow-up, which shows optimal left ventricle recovery with no perioperative or postoperative complications, thus supporting a wider application of the operation.

Adult↗