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Biomedical subjects

J G Grandjean

Publications and source records attributed to J G Grandjean.

At least 19 recordsLinked to original sources

Endoventriculoplasty using autologous endocardium for anterior left ventricular aneurysms.

BACKGROUND: There is currently consensus that endoventriculoplasty is the treatment of choice for an anterior left ventricular aneurysm. We describe here a new technique of endoventriculoplasty using autologous endocardium for left ventricular anterior aneurysm. METHOD: From 1990 until 2003, 49 patients underwent endoventriculoplasty using autologous pericardium at the Thoraxcenter of the University Hospital of Groningen in the Netherlands (28 patients) and at the Department of Cardio Thoracic Surgery of the University Hospital of Pisa in Italy (21 patients). Mean logistic EuroSCORE and mean ejection fraction were 15.7 +/- 6.7 and 31 +/- 9 %, respectively. RESULTS: Overall 30-day mortality was 4.1 %. Causes of in-hospital mortality were low output syndrome (1 patient) and ventricular fibrillation (1 patient). Postoperative complications were myocardial infarct (4.1 %), low output syndrome (6.1 %), renal failure (4.1 %), neurological events (2.0 %), atrial fibrillation (14.3 %), ventricular fibrillation or tachycardia (6.1 %), ARDS (4.1 %), re-operation for bleeding (4.1 %), and major wound infection (2.0 %). CONCLUSION: Our analysis shows that endoventriculoplasty with autologous endocardium is a safe procedure and improves the outcome in high-risk patients with ventricular aneurysm.

Aged↗

Effects of quinapril on clinical outcome after coronary artery bypass grafting (The QUO VADIS Study). QUinapril on Vascular Ace and Determinants of Ischemia.

The QUO VADIS study was designed to explore whether 1 year of angiotensin-converting enzyme inhibition with quinapril (40 mg/day) would decrease ischemia in patients who underwent coronary artery bypass grafting (CABG). Patients (n = 149) scheduled for CABG were randomized 4 weeks before surgery. Study medication was used from randomization up to 1 year after CABG. Exercise testing was performed at randomization; the exercise test was repeated 1 year after CABG and patients underwent 48-hour Holter monitoring. Clinical ischemic events were recorded and defined as death, revascularization, myocardial infarction, recurrence of angina pectoris, ischemic stroke, or transient ischemic attack. Baseline characteristics were similar between groups. Total exercise time increased overall by 75 +/- 76 seconds 1 year after CABG (placebo +79 +/- 75 seconds, quinapril +72 +/- 79 seconds, p = 0.6). All patients had ischemic ST-segment changes at randomization; 33% of patients had ischemic ST-segment changes 1 year after CABG (placebo 29%, quinapril 37%, p = 0.4). On Holter monitoring, the number of patients experiencing > or = 1 episodes of ischemia was equal in both groups. Treatment with quinapril significantly reduced clinical ischemic events after CABG: 15% in patients on placebo versus 4% of patients on quinapril (hazard ratio 0.23, 95% confidence interval 0.06 to 0.87, p = 0.02). Long-term quinapril treatment significantly reduced clinical ischemic events within 1 year after CABG, although ischemia at exercise testing and Holter monitoring was unchanged.

Aftercare↗

Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels.

OBJECTIVES: Our purpose was to determine whether patients with persistent atrial fibrillation (AF) and patients with paroxysmal AF show alterations in potassium channel expression. BACKGROUND: Persistent AF is associated with a sustained shortening of the atrial action potential duration and atrial refractory period. Underlying molecular changes have not been studied in humans. We investigated whether a changed gene expression of specific potassium channels is associated with these changes in patients with persistent AF and in patients with paroxysmal AF. METHODS: Right atrial appendages were obtained from 8 patients with paroxysmal AF, 10 with persistent AF and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass surgery, whereas most AF patients underwent Cox's MAZE surgery (atrial arrhythmia surgery to cure AF) (n = 12). All patients had normal left ventricular function. mRNA (ribonucleic acid) levels were measured by semiquantitative polymerase chain reaction and protein content by Western blotting. RESULTS: mRNA levels of transient outward channel (Kv4.3), acetylcholine-dependent potassium channel (Kir3.4) and ATP-dependent potassium channel (Kir6.2) were reduced in patients with persistent AF (-35%, -47% and -36%, respectively, p < 0.05), whereas only Kv4.3 mRNA level was reduced in patients with paroxysmal AF (-29%, p = 0.03). No changes were found for Kv1.5 and HERG mRNA levels in either group. Protein levels of Kv4.3, Kv1.5 and Kir3.1 were reduced both in patients with persistent AF (-39%, -84% and -47%, respectively, p < 0.05) and in those with paroxysmal AF (-57%, -64%, and -40%, respectively, p < 0.05). CONCLUSIONS: Persistent AF is accompanied by reductions in mRNA and protein levels of several potassium channels. In patients with paroxysmal AF these reductions were observed predominantly at the protein level and not at the mRNA level, suggesting a post-transcriptional regulation.

Aged↗

Ion channel remodeling is related to intraoperative atrial effective refractory periods in patients with paroxysmal and persistent atrial fibrillation.

BACKGROUND: Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF. METHODS AND RESULTS: mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca(2+) channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation. CONCLUSIONS: AF is predominantly accompanied by decreased protein contents of the L-type Ca(2+) channel and several potassium channels. Reductions in L-type Ca(2+) channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF.

Atrial Fibrillation↗

Electrical remodeling and atrial dilation during atrial tachycardia are influenced by ventricular rate: role of developing tachycardiomyopathy.

INTRODUCTION: Atrial fibrillation (AF) and congestive heart failure (CHF) are two clinical entities that often coincide. Our aim was to establish the influence of concomitant high ventricular rate and consequent development of CHF on electrical remodeling and dilation during atrial tachycardia. METHODS AND RESULTS: A total of 14 goats was studied. Five goats were subjected to 3:1 AV pacing (A-paced group, atrial rate 240 beats/min, ventricular rate 80 beats/min). Nine goats were subjected to rapid 1:1 AV pacing (AV-paced group, atrial and ventricular rates 240 beats/min). During 4 weeks, right atrial (RA) and left ventricular (LV) diameters were measured during sinus rhythm. Atrial effective refractory periods (AERP) and inducibility of AF were assessed at three basic cycle lengths (BCL). After 4 weeks of rapid AV pacing, RA and LV diameters had increased to 151% and 113% of baseline, whereas after rapid atrial pacing alone, these parameters were unchanged. Right AERP (157+/-10 msec vs 144+/-16 msec at baseline with BCL of 400 msec in the A-paced and AV-paced group, respectively) initially decreased in both groups, reaching minimum values within 1 week. Subsequently, AERP partially recovered in AV-paced goats, whereas AERP remained short in A-paced goats (79+/-7 msec vs 102+/-12 msec after 4 weeks; P < 0.05). Left AERP demonstrated a similar time course. Inducibility of AF increased in both groups and reached a maximum during the first week in both groups, being 20% and 48% in the A-paced and AV-paced group, respectively. CONCLUSION: Nature and time course of atrial electrical remodeling and dilation during atrial tachycardia are influenced by concurrent high ventricular rate and consequent development of CHF.

Animals↗

Continued cigarette smoking after coronary artery bypass surgery reduces endothelium-dependent vasodilation in internal thoracic artery grafts.

BACKGROUND: Cigarette smoking is known to promote endothelial dysfunction, thus it can be responsible for an impaired endothelium-dependent vasomotility in arterial grafts late after coronary surgery. METHODS: Twenty consecutive patients (mean age 64.5 years), previously submitted to coronary bypass surgery with the internal thoracic artery, underwent quantitative angiography of the implanted graft at long-term follow-up (mean time 2.5 years). To assess both endothelium-dependent and independent vasomotility, angiograms were acquired before and after selective infusions of acetylcholine (10(-6) mmol/ml) and nitroglycerine (500 microg). The predictive value of risk factors, including previous and continued smoking, for an impairment in endothelium-dependent vasomotility was assessed. RESULTS: Continued smoking (p = 0.038), but not a previous history of smoking (p = 0.55) was the only predictor of a reduced endothelium-dependent vasodilation. While previous smokers and non-smokers showed a similar response to acetylcholine, current smokers showed a reduced endothelium-dependent vasodilation vs non-smokers (94.8 +/- 2.6 vs 99.6 +/- 2.3% of the maximal vasodilative capacity, p = 0.001). CONCLUSIONS: Although maintained, the vasodilative response to acetylcholine appears reduced in internal thoracic artery grafts of patients who continued smoking long term after coronary bypass surgery. Whether this could affect the long-term outcome of these patients has to be further investigated.

Acetylcholine↗

Angiographic evidence of thrombosis after off-pump coronary surgery. A case report.

We report the case of a patient who underwent off-pump coronary surgery, whose postoperative (3 days) angiography showed the presence of a thrombus in the left internal mammary artery. The thrombus responded to an aggressive anticoagulant treatment, showing a perfect angiographic result 15 months later. According to our previous studies, we suggest that an adequate anti-coagulant treatment should be undertaken for patients undergoing off-pump coronary surgery in the early postoperative period.

Coronary Angiography↗

Reversed-T upper mini-sternotomy for extended thymectomy in myasthenic patients.

A minimally invasive approach for extended thymectomy in myasthenic patients is described. Through an 8- to 10-cm midline skin incision with a reversed-T upper mini-sternotomy, an extended thymectomy was performed. The mediastinal fat was removed beginning from the diaphragm up to the thyroid gland, and to each phrenic nerve, laterally. Extended thymectomy through a reversed-T upper mini-sternotomy warrants complete excision of thymic tissue while allowing a short hospitalization and good cosmetic result.

Adult↗

Functional integrity and aging of the left internal thoracic artery after coronary artery bypass surgery.

OBJECTIVE: To study the endothelial function in the left internal thoracic artery after coronary artery bypass surgery and to identify predictors of early dysfunction, we performed a provocative test with acetylcholine in 23 male patients who underwent routine postoperative coronary angiography. METHODS: The change in mean diameter of the proximal thoracic artery was assessed by quantitative angiography after selective injections of acetylcholine and nitroglycerin. RESULTS: The thoracic artery showed a 6.8% (P <. 001) and 9.0% (P <.001) increase in mean diameter after acetylcholine and nitroglycerin administration, respectively. Vasodilative responses to acetylcholine and nitroglycerin administration were strongly correlated (R: 0.88; P <.001). Among the common risk factors, only age was associated with an impairment in the vasodilative response of the arterial graft (P =.001), and acetylcholine-induced vasodilation was inversely correlated to the age of the patient (R: 0.69; P <.001). CONCLUSIONS: Endothelium-dependent vasodilative response to acetylcholine administration seems well preserved in the left internal thoracic artery after surgery. Common risk factors, except for age, do not affect the functional integrity of the arterial graft. The vasodilative properties of the graft depend on the age of the patient and do not deteriorate over time after operation.

Acetylcholine↗

Mini-maze suffices as adjunct to mitral valve surgery in patients with preoperative atrial fibrillation.

INTRODUCTION: After mitral valve (MV) surgery, preoperative atrial fibrillation (AF) often recurs while cardioversion therapy generally fails. Additional Cox maze surgery improves postoperative arrhythmia outcome, but the extensive nature of such an approach limits general appliance. We investigated the clinical outcome of a simplified, less extensive Cox maze procedure ("mini-maze") as adjunct to MV surgery. METHODS AND RESULTS: Thirteen patients with MV disease and preoperative AF were treated with combined surgery (group 1). Nine control patients without previous AF underwent isolated MV surgery (group 2). We retrospectively compared the results to findings in 23 patients with preoperative AF who had undergone isolated MV surgery (group 3). In group 1, mini-maze took an additional 46 minutes of perfusion time. One 75-year-old patient died of postoperative multiple organ failure. Seven patients showed spontaneously converting (within 2 months) postoperative AF. After 1 year, 82% were in sinus rhythm (SR). No sinus node dysfunction was observed. In group 2, all patients were in SR after 1 year. In group 3, only 53% were in SR after 1 year, despite serial cardioversion and antiarrhythmic drug therapy. Exercise tolerance and heart rate were comparable for groups 1 and 2. Left atrial function was present in all but one patient in group 1 and in all patients in group 2 (after MV reconstruction). CONCLUSION: Adding a relatively simple mini-maze to MV surgery improves arrhythmia outcome in patients with preoperative AF without introducing sinus node dysfunction or persistent absence of left atrial function. The results of this type of combined surgery are encouraging and deserve further attention.

Aged↗

Arterial conduits for myocardial revascularization: single-institutional results.

BACKGROUND: Bilateral internal mammary artery (IMA) grafting is associated with an improved long-term survival, low rates of recurrence of angina and late myocardial infarction. This suggested the usefulness of a complete arterial revascularization in patients with three-vessel disease using IMAs in conjunction with other arterial conduits. METHODS: Between September 1989 and September 1999, 1,052 patients underwent myocardial revascularization with the use of the gastroepiploic artery and one or two IMAs. Among them 561 patients with three-vessel disease underwent myocardial revascularization with the use of the gastroepiploic artery and both the IMAs. In this report the operative results up to hospital discharge obtained in the first 500 patients were considered. In total 1,850 anastomoses were performed using 1,500 arterial grafts; a mean number of 3.7 anastomoses per patient and 1.2 anastomoses per graft were performed. RESULTS: Twelve patients (2.4%) died during hospitalization. Perioperative myocardial infarction developed in 12 patients (2.4%). Twenty patients (4%) required temporary support with intra-aortic balloon pump. Repeat thoracotomy for bleeding was required in 33 patients (6.6%). Four patients (0.8%) developed mediastinitis and 4 (0.8%) aseptic sternal dehiscence. Gastrointestinal bleeding occurred in 3 patients (0.6 %) and was treated conservatively, cerebrovascular accidents in 4 (0.8%), and abdominal wound herniation in 5 (1%). CONCLUSIONS: According to our experience, systematic total arterial revascularization is feasible with a low complication rate and may contribute to the improvement of long-term outcome.

Aged↗

Digoxin delays recovery from tachycardia-induced electrical remodeling of the atria.

BACKGROUND: Atrial fibrillation (AF) induces electrical remodeling, which is thought to be responsible for the low success rate of antiarrhythmic treatment in AF of longer duration. Electrical remodeling seems to be related to tachycardia-induced intracellular calcium overload. Due to its vagomimetic action, digoxin is widely used to control the ventricular rate during AF, but it also increases intracellular calcium. On the basis of these characteristics, we hypothesized that digoxin would aggravate tachycardia-induced electrical remodeling. METHODS AND RESULTS: We analyzed the atrial effective refractory period (AERP) at cycle lengths of 430, 300, and 200 ms during 24 hours of rapid atrio/ventricular (300/150 bpm) pacing in 7 chronically instrumented conscious goats treated with digoxin or saline. Digoxin decreased the spontaneous heart rate but had no other effects on baseline electrophysiological characteristics. In addition to a moderate increase in the rate of electrical remodeling during rapid pacing, digoxin significantly delayed the recovery from electrical remodeling after cessation of pacing (at 430, 300, and 200 ms: P=0. 001, P=0.0015, and P=0.007, respectively). This was paralleled by an increased inducibility and duration of AF during digoxin. Multivariate analysis revealed that both a short AERP and treatment with digoxin were independent predictors of inducibility (P=0.001 and P=0.03, respectively) and duration (P=0.001 for both) of AF. CONCLUSIONS: Dioxin aggravates tachycardia-induced atrial electrical remodeling and delays recovery from electrical remodeling in the goat, which increases the inducibility and duration of AF.

Animals↗

Reversed-J inferior sternotomy for beating heart coronary surgery.

Median sternotomy or combined multiple minimally invasive approaches are currently used to revascularize patients with multivessel coronary artery disease on the beating heart. We present here a new alternative approach for minimally invasive coronary surgery on the beating heart: the reversed-J inferior sternotomy. Through this approach, the left anterior descending, diagonal, and right coronary arteries can be revascularized via a single minimally invasive approach.

Coronary Disease↗

Procoagulant activity after off-pump coronary operation: is the current anticoagulation adequate?

BACKGROUND: Hemostasis is preserved after off-pump coronary operations compared with conventional coronary procedures. However, this preserved hemostasis may result in a procoagulant activity. METHODS: We prospectively studied coagulation in 22 patients who underwent off-pump coronary operation either through a midline sternotomy (n = 14) or with minimally invasive anterolateral thoracotomy (n = 8). RESULTS: Procoagulant activity, represented by prothrombin factor 1 and 2, remained at baseline levels during operation but increased significantly on postoperative day 1. Factor VII remained at baseline levels during the operation but decreased significantly on postoperative day 1. Fibrinolysis was increased as indicated by the fibrin degradation products on postoperative day 1. A promoted hemostasis attributable to endothelial activation was indicated by the increase in von Willebrand factor on postoperative day 1. Platelets counts and platelet activation (beta-thromboglobulin) remained at baseline levels after the operation. No adverse clinical events occurred. CONCLUSIONS: Patients undergoing off-pump coronary operation show an increased procoagulant activity in the first postoperative 24 hours regardless of the surgical approach (midline sternotomy or anterolateral thoracotomy). This procoagulant activity is not mediated by platelet-related factors. Therefore, a specific perioperative prophylactic pharmacologic regimen is advisable.

Adult↗

Gene expression of proteins influencing the calcium homeostasis in patients with persistent and paroxysmal atrial fibrillation.

OBJECTIVE: Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS: Right atrial appendages were obtained from eight patients with paroxysmal AF, ten with persistent AF (> 8 months) and 18 matched controls in sinus rhythm. All controls underwent coronary artery bypass grafting, whereas most AF patients underwent Cox's MAZE surgery (n = 12). All patients had a normal left ventricular function. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction the cDNA of interest and of glyceraldehyde-3-phosphate dehydrogenase were coamplified and separated by ethidium bromide-stained gel electrophoresis. Slot blot analysis was performed to study protein expression. RESULTS: L-type calcium channel alpha 1 and sarcoplasmic reticulum Ca(2+)-ATPase mRNA (-57%, p = 0.01 and -28%, p = 0.04, respectively) and protein contents (-43%, p = 0.02 and -28%, p = 0.04, respectively) were reduced in patients with persistent AF compared to the controls. mRNA contents of phospholamban, ryanodine receptor type 2 and sodium/calcium exchanger were comparable. No changes were observed in patients with paroxysmal AF. CONCLUSIONS: Alterations in gene expression of proteins involved in the calcium homeostasis occur only in patients with long-term persistent AF. In the absence of underlying heart disease, the changes are rather secondary than primary to AF.

Aged↗

Tachycardia induced electrical remodeling of the atria and the autonomic nervous system in goats.

Atrial fibrillation (AF) shortens the atrial effective refractory period (AERP). To investigate the role of the autonomic nervous system during this so-called electrical remodeling of the atria (ERA) and during recovery from ERA we analyzed heart rate variability (HRV). In 12 goats atrioventricular (300:150 beats/min) pacing was performed for 24 hours, interrupted at 4, 8, 16, and 24 hours for recording of 500 atrial (AA) intervals during sinus rhythm and measurement of the AERP(430ms) at 7.4 +/- 0.6 sites. After 24 hours, pacing was stopped and the electrophysiological study and recording of the AA intervals was repeated at 4, 8, 16, and 24 hours after cessation of pacing. Time- and frequency-domain parameters were computed from each 500 AA interval recording. After 24 hours of rapid pacing the AERP had shortened significantly (147 +/- 5.6 to 102+/- 6.4 ms, P < 0.0001). No significant changes in HRV and dispersion of refractoriness (AAERP) (47 +/- 7.1 to 44 +/- 4.2 ms) were observed. After cessation of pacing, the AERP prolonged again (102 +/-6.4 to 135+/-8.8 ms, P < 0.0001) and was paralleled by a significant increase in AAERP (44 +/- 4.2 to 63+/- 7.1 ms, P = 0.01). Furthermore, HRV increased significantly. At each time point an inverse relation between the logarithmically transformed vagal parameter HF (InHF) and AERP was observed. We calculated the mean InHF for each goat using all time points and used the median value to divide the 12 goats into high and low vagal tone groups. We compared the degree of ERA and recovery from ERA for both groups. The AERP shortened 47.4 +/- 6.5 versus 43.0+/-5.0 ms (NS) for goats with high and low vagal tone, respectively. During recovery from ERA the AERP lengthened 23.6 +/- 4.0 versus 42.5 +/- 1.7 ms (P = 0.001) for goats with high and low vagal tone, respectively. Multivariate regression analysis indicated a short AERP as the single independent determinant of the inducibility of AF during ERA and recovery from ERA (P < 0.0001). During recovery from ERA, the AERP prolonged and vagal tone and AAERP increased. A high vagal tone during recovery from ERA was associated with a short AERP and an attenuated recovery of ERA.

Animals↗