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Biomedical subjects

Hendrik T Tevaearai

Publications and source records attributed to Hendrik T Tevaearai.

At least 19 recordsLinked to original sources

Leakage of the arterial prosthesis of an Impella RVAD.

Seromas occurring around a vascular graft are a rare complication. We report a life-threatening plasma leakage that occurred through the polytetrafluoroethylene vascular prosthesis of an Impella right ventricular assist device (Impella RD [Impella Cardiosystems GmbH, Aachen, Germany]) implanted in a 62-year-old patient with acute right ventricular failure after cardiac transplantation. The leakage became progressively massive. Weaning the patient from the right ventricular assist device was not possible. The prosthesis was thus wrapped within a pericardial patch to contain the leakage. Three days later the patient could be successfully weaned and the pump was removed. The clinical evolution was favorable.

Biocompatible Materials↗

Myoblast-seeded biodegradable scaffolds to prevent post-myocardial infarction evolution toward heart failure.

OBJECTIVE(S): Even though the mechanism is not clearly understood, direct intramyocardial cell transplantation has demonstrated potential to treat patients with severe heart failure. We previously reported on the bioengineering of myoblast-based constructs. We investigate here the functional outcome of infarcted hearts treated by implantation of myoblast-seeded scaffolds. METHODS: Adult Lewis rats with echocardiography-confirmed postinfarction reduced ejection fraction (48.3% +/- 1.1%) were randomized to (1) implantation of myoblast-seeded polyurethane patches at the site of infarction (PU-MyoB, n = 11), (2) implantation of nonseeded polyurethane patches (PU, n = 11), (3) sham operation (Sham, n = 12), and (4) direct intramyocardial myoblast injection (MyoB, n = 11). Four weeks later, the functional assessment by echocardiography was repeated, and we additionally performed left ventricular catheterization plus histologic studies. RESULTS: The ejection fraction significantly decreased in the PU (39.1% +/- 2.3%; P = .02) and Sham (39.9% +/- 3.5%; P = .04) groups, whereas it remained stable in the PU-MyoB (48.4% +/- 3.1%) and MyoB (47.9% +/- 3.0%) groups during the observation time. Similarly, left ventricular contractility was significantly higher in groups PU-MyoB (4960 +/- 266 mm Hg/s) and MyoB (4748 +/- 304 mm Hg/s) than in groups PU (3909 +/- 248 mm Hg/s, P = .01) and Sham (4028 +/- 199 mm Hg/s, P = .01). Immunohistology identified a high density of myoblasts within the seeded scaffolds without any migration toward the host cardiac tissue and no evidence of cardiac cell differentiation. CONCLUSIONS: Myoblast-seeded polyurethane scaffolds prevent post-myocardial infarction progression toward heart failure as efficiently as direct intramyocardial injection. The immunohistologic analysis suggests that an indirect mechanism, potentially a paracrine effect, may be assumed.

Animals↗

Effect of acute body positional changes on the haemodynamics of rats with and without myocardial infarction.

In humans, the lateral recumbent position has a beneficial effect on haemodynamics. If this effect is substantial in small animals too, there is a risk of misinterpretation in preclinical investigations. Therefore, the aim of this study was to analyse the impact of acute changes in body position on haemodynamics in rats. Healthy rats (n=21) and rats post myocardial infarction (n=20) were randomly positioned supine, prone, or on the right or left side. In each position, we measured haemodynamic parameters by pressure-tip catheter and thermodilution. We found that left ventricular contractility (dP/dtmax) was significantly elevated in both lateral positions as compared to the supine position in healthy rats. In healthy rats and following infarction, cardiac index (CI) and stroke volume index (SVI) were significantly higher in both lateral positions as compared to the supine or prone position. Of importance, if SVI values in the supine position in healthy rats (0.095 +/- 0.003 ml (100 g)(-1)) are compared to SVI values measured in different positions after myocardial infarction, the SVI can be either significantly lower in the supine (0.084 +/- 0.003 ml (100 g)(-1)) or significantly higher in the left lateral position (0.105 +/- 0.003 ml (100 g)(-1)). We conclude that post myocardial infarction and in healthy control rats, important haemodynamic values are increased in lateral positions as compared to prone or supine positions. Analysing haemodynamic data in rats may therefore result in misinterpretation if the body position is inconsistent.

Algorithms↗

Acute ischemic cardiac dysfunction is attenuated via gene transfer of a peptide inhibitor of the beta-adrenergic receptor kinase (betaARK1).

Acute myocardial ischemia is a critical adverse effect potentially occurring during cardiac procedures. A peptide inhibitor of the beta-adrenergic receptor kinase (betaARK1), betaARKct, has been successful in rescuing chronic myocardial ischemia. The present study focused on the effects of adenoviral-mediated betaARKct (Adv-betaARKct) delivery on left ventricle (LV) dysfunction induced by acute coronary occlusion. Rabbits received intracoronary delivery of phosphate-buffered saline (PBS) (n=9) or 5x10(11) viral particles of betaARKct (n=8). A loose prolene 5-0 Potz-loop suture was placed around the circumflex coronary artery (LCx) with both ends buried under the skin. Four days later, the suture was retrieved and pulled to occlude the LCx. Ischemia was confirmed by immediate ECG changes. LV function was continuously recorded for 45 min. Contractility (LVdP/dtmax), relaxation (LVdP/dtmin) and end diastolic pressure (EDP) were less impaired in the betaARKct group as compared to PBS (P<0.05, two-way ANOVA). betaAR density was higher in the ischemic area of the LV in the betaARKct group (betaARKct: 71.9+/-4.6 fmol/mg protein, PBS: 54.5+/-4.0 fmol/mg protein, P<0.05). Adenylyl cyclase activity was also improved basally and in response to betaAR stimulation. betaARK1 activation was less in the betaARKct group (P<0.05). Therefore, inhibition of myocardial betaARK1 may represent a new strategy to prevent LV dysfunction induced by acute coronary ischemia.

Adenoviridae↗

Molecular restoration of beta-adrenergic receptor signaling improves contractile function of failing hearts.

beta-adrenergic receptor (betaAR) antagonists, or beta blockers, are now a part of the standard therapeutic arsenal in the medical management of chronic heart failure (HF). Conversely, betaAR stimulation remains the most efficient way to enhance cardiac contractile function acutely, although long-term inotropic therapy based on enhanced betaAR stimulation is likely detrimental. Although altered betaAR signaling plays a pivotal role in the genesis of HF, the choice to therapeutically agonize or antagonize this receptor pathway remains an area of ongoing investigation. Research from the authors' laboratory as well as other research conducted over the last 10 years has produced evidence to support the fact that "normalizing" the betaAR system at a molecular level and improving signaling, instead of blocking it, leads to significant enhancement of cardiac contractile function and prevents ventricular remodeling in HF. This review summarizes the extensive in vivo animal model experimentation that supports the still-controversial hypothesis that increasing the myocardial density of beta(2)-ARs or, more effectively, inhibiting the activity of the betaAR kinase (also referred to as G-protein-coupled receptor kinase 2), represent potential novel therapeutic strategies for HF.

Adrenergic beta-Antagonists↗

High prevalence of unsuspected abdominal aortic aneurysms in patients hospitalised for surgical coronary revascularisation.

OBJECTIVES: Prevalence of abdominal aortic aneurysms (AAA) is not exactly known among patients with coronary artery disease (CAD) who are considered for surgical revascularisation. We evaluated the value of screening AAA among coronary patients admitted in our cardiovascular surgery unit. METHODS: Over a 24-month period, an abdominal echography was proposed to male patients aged 60 or more while hospitalised for surgical coronary revascularisation. Patients with previous investigation of the aorta were excluded. The aorta was considered aneurysmal when the anterior-posterior diameter was of 30 mm or more. RESULTS: Three hundred and ninety-five consecutive patients all accepted a proposed abdominal echographic screening for AAA. Forty unsuspected AAA were detected (10.1%). The mean diameter was 38.9 +/- 1.3 mm. Four AAA were larger than 50 mm and considered for surgery after the CABG procedure. Surveillance was proposed to the other 36, especially the 10 patients with an AAA larger than 40 mm. Patients with AAA were significantly older than those without AAA (71.3 +/- 0.8 vs. 69.4 +/- 0.3 years, P<0.05). Smoking history (P<0.05) and hypertension (P<0.05) were also associated more frequently with AAA. More than 16% of the patients being smokers and suffering hypertension presented with unsuspected AAA. CONCLUSIONS: In-hospital screening of AAA is very efficient among patients with coronary artery disease. Therefore, patients with CAD may be considered for routine AAA screening.

Aged↗

Limitations using the vacuum-assist venous drainage technique during cardiopulmonary bypass procedures.

Vacuum-assist venous drainage (VAVD) can increase venous blood return during cardiopulmonary bypass (CPB) procedures. However, the negative pressure created in the closed cardiotomy reservoir can be transmitted to the oxygenator if a nonocclusive or centrifugal arterial pump is used, resulting in bubble transgression (BT) from the gas to blood compartment of the oxygenator. We analyzed the vacuum pressure required to produce BT using an in vitro circuit including successively a closed reservoir, a pump (centrifugal or roller), and an oxygenator. A constant hydrostatic pressure was maintained onto the oxygenator. Vacuum was applied on the cardiotomy reservoir, progressively increasing negative pressure from 0 to -80 mmHg and monitoring BT with a bubble detector. Six different oxygenators were compared. A partially occlusive roller pump and a centrifugal pump were compared to a control, which was without any pump. A mean negative pressure of -53 +/- 7 mmHg was necessary to produce BT in all the oxygenators in the absence of a pump. The presence of a centrifugal pump between the reservoir and the oxygenator significantly increased the negative pressure required to produce BT compared to the control (-67 +/- 7 mmHg, p < .05). No bubbles were detected using the roller pump (> -80 mmHg needed for BT), thus statistically significant when compared to the centrifugal pump (p < .05). The centrifugal pump offers significant resistance to BT but not as much compared to the roller pump, though BT cannot be prevented if the pump is turned off while the vacuum remains on the reservoir. Therefore, VAVD is a safe technique as long as the perfusionist stops the vacuum when the arterial pump is no longer in use.

Adult↗

Myocardial gene transfer and overexpression of beta2-adrenergic receptors potentiates the functional recovery of unloaded failing hearts.

BACKGROUND: Mechanical assistance of the failing left ventricle (LV) can lead to functional recovery after a period of unloading, including restoration of beta-adrenergic receptor (betaAR) inotropic reserve. We tested whether prolonged LV unloading of failing rabbit hearts by use of a heterotopic transplantation technique could lead to recovery and whether adenoviral gene transfer of a beta2AR transgene (Adv-beta2AR) could alter this process. METHODS AND RESULTS: Heart failure was induced by coronary artery ligation in adult New Zealand White rabbits. After 4 weeks, failing hearts were heterotopically transplanted into recipient rabbits, allowing normal coronary perfusion but complete LV unloading. We also placed an LV latex balloon for remote access and in vivo physiological analysis. We found that there was reversal of signaling and functional abnormalities after 30 days of unloading. In another set of failing hearts, we randomly delivered, at the time of transplantation, either 2x10(11) viral particles of Adv-beta2AR or saline via the coronary arteries. Sham-operated animals with nonfailing hearts served as controls. After 5 days of unloading, in vivo LV contractility (LV dP/dt(max)) and relaxation (LV dP/dt(min)) were significantly decreased in saline-treated failing hearts compared with control nonfailing hearts (P<0.05). In failing hearts treated with Adv-beta2AR, however, LV dP/dt(max) and LV dP/dt(min) were improved in response to higher preloads (P<0.05) and betaAR stimulation (P<0.01). CONCLUSIONS: Heterotopic transplantation in the rabbit does allow recovery of the failing heart, and beta2AR overexpression acutely enhances this functional improvement. Accordingly, genetic manipulation of betaAR signaling may represent a novel molecular adjunct to mechanical assistance to facilitate functional myocardial recovery.

Adenoviridae↗

Atrial fibrillation and minimally invasive coronary artery bypass grafting: risk factor analysis.

Atrial fibrillation (AF) is a frequent arrhythmia after conventional coronary artery bypass grafting. With the advent of minimally invasive technique for left internal mammary artery-left anterior descending coronary artery (LIMA-LAD) grafting, we analyzed the incidence and the risk factors of postoperative AF in this patient population. This prospective study involves all patients undergoing isolated LIMA-LAD grafting with minimally invasive technique between January 1994 and June 2000. Twenty-four possible risk factors for postoperative AF were entered into univariate and multivariate logistic regression analyses. Postoperative AF occurred in 21 of the 90 patients (23.3%) analyzed. Double- or triple-vessel disease was present in 12/90 patients (13.3%). On univariate analysis, right coronary artery disease (p <0.01), age (p = 0.01), and diabetes (p = 0.04) were found to be risk factors for AF. On multivariate analysis, right coronary artery disease was identified as the sole significant risk factor (p = 0.02). In this patient population, the incidence of AF after minimally invasive coronary artery bypass is in the range of that reported for conventional coronary artery bypass grafting. Right coronary artery disease was found to be an independent predictor, and this may be related to the fact that in this patient population the diseased right coronary artery was not revascularized at the time of the surgical procedure. For the same reason, this risk factor may find a broader application to noncardiac thoracic surgery.

Aged↗

A new expandable venous cannula for minimal access heart surgery.

BACKGROUND: During percutaneous cannulation, the diameter of the venous cannula is determined by the size of the access site. To limit this restriction, the Smart cannula (Cardiosmart Ltd., Fribourg, Switzerland) has been developed. Because its design allows self-expansion within the recipient vein, diameter restriction is limited to the access site. METHODS: In 6 calves (78 +/- 4.3 kg), the jugular vein and the carotid artery were cannulated through a cervicotomy. The Smart cannula was tested against three percutaneous cannulas with a diameter of 27, 25, and 21F, respectively. Stenotic percutaneous access to the vein was simulated by 1-cm wide tape encircling the vein that could be adjusted to a diameter of 27, 25, and 21F, respectively. The maximal flow rate, reached with stable reservoir level and a negative pressure of 44 mm Hg, was determined three times for each access size with the Smart cannula (one size fits all) and the corresponding percutaneous cannula successively. RESULTS: For an access size of 27F, the flow of the Smart cannula was 5.7 +/- 0.4 L/min and that of the percutaneous cannula was 4.3 +/- 0.2 L/min (p < 0.0001); for 25F, flow rates were 5.6 +/- 0.5 and 3.9 +/- 0.2 L/min, respectively (p < 0.0001); and for 21F, the flow rates were 4.3 +/- 0.4 and 2.7 +/- 0.3 L/min, respectively (p < 0.0001). The percentage increase of flow for the 27, 25, and 21F sizes were 34% +/- 9%, 42% +/- 16%, and 53% +/- 18%, respectively (one-way analysis of variance, p = 0.014). CONCLUSIONS: For the present set-up, the Smart cannula outperforms commercially available percutaneous cannulas. The smaller the size of the insertion site, we observed a higher gain of flow with the Smart cannula.

Animals↗

Hemodynamics optimization during off-pump coronary artery bypass: the 'no compression' technique.

OBJECTIVE: Heart manipulation during OPCAB may cause hemodynamical instability in particular for access to the posterior and lateral walls. The 'no compression' technique involves enucleation of the heart without any compression on the cavities, and stabilization of the target area with a suction device. The impact of this technique on hemodynamics is assessed. METHODS: In order to analyze a homogeneous group, 26 consecutive patients with triple grafts, one to each side of the heart in the same sequential order (posterior, lateral and anterior wall successively) were selected. Heart rate (HR), mean pulmonary arterial pressure (PAP, mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), mean arterial pressure (MAP, mmHg), cardiac output index (COI, l/min per m(2)), and central venous saturation (SvO(2),%) were monitored. A coronary shunt was used for all the anastomoses. RESULTS: HR was stable with baseline value of 60+/-10 and the highest value for the anterior wall, 63.6+/-8 (P=0.23). PAP and PCWP exhibited their highest increase, when compared with baseline, for the lateral wall, 23.9+/-4.7 vs. 20.7+/-6.2 (P=0.06), and 17.2+/-4.7 vs. 14.9+/-5.6 (P=0.16), respectively. MAP, COI and SvO(2), exhibited their largest drop, when compared with baseline, for the lateral wall too, 73.1+/-9.1 vs. 77.1+/-7.5 (P=0.12), 1.99+/-0.47 vs. 2.26+/-0.55 (P=0.09), and 70.5+/-8.4 vs. 74.8+/-9.3 (P=0.12), respectively. CONCLUSIONS: None of the hemodynamical parameter differed significantly from baseline value for all three territories. While hemodynamics was perfectly maintained during the posterior and anterior walls revascularization, exposure of the lateral wall led to marginal changes only.

Aged↗

Donor heart contractile dysfunction following prolonged ex vivo preservation can be prevented by gene-mediated beta-adrenergic signaling modulation.

OBJECTIVES: Reperfusion after myocardial ischemia goes together with alteration of the beta-adrenergic (betaAR) signaling. Especially the level and catalytic activity of beta AR kinase (betaARK1) are increased. We hypothesized that myocardial expression of a betaARK1 inhibitor (betaARKct) may protect from post-reperfusion dysfunction. METHODS: Two groups of rabbits were treated by intracoronary delivery of either phosphate-buffered saline (PBS) or a solution of adenovirus carrying the betaARKct transgene (Adeno-betaARKct). At day 5, the hearts were explanted after cold cardioplegic arrest, and preserved at 4 degrees C for 4 h. Reperfusion was hemodynamically standardized on a Langendorff apparatus with oxygenated Krebs solution for 30 min before left ventricular (LV) pressure was recorded using an LV latex balloon connected to a pressure transducer. Non-arrested hearts immediately perfused on the Langendorff apparatus served as controls. RESULTS: LV contractility (LV dP/dt(max), P < 0.05) and relaxation (LV dP/dt(min), P < 0.05) were reduced, and end diastolic pressure (LV EDP) was increased after prolonged exposure to cold preservation solution as compared to normal control hearts, both under basal conditions and when stimulated with the betaAR agonist isoproterenol. However, these parameters remained within a normal range in Adeno-betaARKct-expressing hearts arrested and preserved for 4 h. Biochemical analysis shows a reduced betaAR density and an impaired signaling after reperfusion of hearts arrested for 4 h whereas it is normalized in Adeno-betaARKct-expressing hearts. CONCLUSION: Myocardial gene-mediated inhibition of betaARK1 via betaARKct expression avoids ventricular dysfunction after prolonged preservation. Therefore, this may represent a way of improving early results of cardiac transplantation and perioperative function.

Adenoviridae↗

Flow dynamic comparison of peripheral venous cannulas used with centrifugal pump assistance in vitro.

Because of the risk of vein collapse, the benefits of using a centrifugal pump to assist venous drainage for cardiopulmonary bypass are limited when the tips of peripheral cannulas are maintained within the vena cava. Using a mock circuit including 20 mm diameter latex tubing to mimic a vena cava, we compared the performance of 6 commercially available peripheral venous cannulas and attempted to determine potential factors influencing maximal flow drainage before vein collapse. A close correlation was observed with the total hole area of the cannula. Best performance (5.10 +/- 0.08 L/min) was obtained with an 8 mm internal diameter (ID) cannula and 343 mm2 total hole area. A larger cannula (ID 9.2 mm) with only 209 mm2 total hole area drained 5.03 +/- 0.05 L/min whereas a smaller cannula (ID 6.7 mm) with a total hole area of 586 mm2 also allowed a similar flow of 5.03 +/- 0.12 L/min. Therefore, the total hole area appears to be a critical factor in designing peripheral cannulas used in restricted chambers such as vena cavae.

Cardiopulmonary Bypass↗

Heterotopic transplantation as a model to study functional recovery of unloaded failing hearts.

OBJECTIVES: Recent studies have demonstrated cardiac improvement in patients supported with a ventricular assist device, suggesting that reverse remodeling and myocardial recovery are possible. We developed an animal model of cardiac unloading by adapting a heterotopic transplantation technique and used it to examine the pattern of functional recovery in the left ventricle of the failing heart. METHODS: Heart failure was induced in adult New Zealand rabbits by coronary artery ligation with subsequent myocardial infarction. Animals undergoing sham operation served as a control group. After 4 weeks or 3 months, failing hearts were transplanted into the necks of recipient rabbits. A left ventricular latex balloon connected to subcutaneous tubing allowed repeated physiologic analysis on days 1 and after transplantation and then every 5 days until day 30. RESULTS: Contractility (left ventricular dP/dt(max)) and relaxation (left ventricular dP/dt(min)) were significantly lower in transplanted postinfarction hearts as compared to control hearts immediately after transplantation. Both left ventricular dP/dt(max) and left ventricular dP/dt(min) responses to increased preload and to beta-adrenergic stimulation progressively improved to a significantly higher level after 30 days of left ventricular unloading for the hearts that were transplanted 4 weeks after myocardial infarction. However, this functional improvement was not detected in failing hearts transplanted 3 months after infarction. CONCLUSIONS: This model of cardiac unloading appears at least partially to mimic conditions of ventricular assist devices. If performed early in the development of heart failure, it permits improvement of contractile dysfunction and restoration of cardiac responsiveness to mechanical and beta-adrenergic stimulation. Therefore this model may constitute a novel alternative in the study of reverse remodeling in unloaded failing hearts.

Animals↗

[ECMO and cardiopulmonary support].

ECMO (extracorporeal membrane oxygenation) may be viewed as a prolonged cardiopulmonary bypass allowing for a prolonged cardio-respiratory support. Since its introduction in the 60's, its indication has expanded from acute respiratory failure to acute cardiac failure refractory to conventional treatments. The target group involves mainly those patients presenting with a cardiogenic shock following cardiac surgery or acute myocardial infarction. The advantages of this form of circulatory support, when compared with long-term ventricular assist devices, are its less invasive aspect, its ease of implantation and its reduced cost. However, its main limitation lies in its limited duration of 7 to 10 days, in particular because of hemorrhage complications. Currently, ECMO provides a temporary hemodynamical stability in order to perform an invasive cardiac treatment (coronary bypass or percutaneous dilatation), or to assess the eligibility of the patient for a long-term ventricular assist device, which will enable to wait for the availability of an allograft. The latter scenario is crucial nowadays because of the severe lack of organ donors, which is the leading cause of death among patients waiting for a heart transplant.

Cardiac Output, Low↗

[Gene therapy and benefits in modulating of system beta-adrenergic in cardiac insufficiency].

Understanding the basic molecular mechanisms that lead to heart failure may allow to define new targets for myocardial gene therapy. In this way, the alterations of the beta-adrenergic signaling that are typically observed in cardiac insufficiency, may be positively modulated by gene manipulation. Both the level and activity of the beta-adrenergic receptor kinase (beta ARK1), a regulatory enzyme that phosphorylates agonist occupied beta-adrenoreceptors, are elevated and account for desensitization of cardiomyocytes to catecholamines. We recently demonstrated that expressing beta ARKct, a peptide which inhibits beta ARK1, allows normalization of contractile function in several animal models of heart failure. This approach may represent a valuable alternative for the treatment of heart failure. The current review summarizes recent studies performed using beta ARKct as a transgene to restore normal beta-adrenergic signaling and improve myocardial function.

Adenoviridae↗

Antithrombotic properties of trillium coated connectors.

Trillium coating (Medtronic Inc., Minneapolis, MN) offers, in addition to the presence of heparin, endothelium-like properties of its negatively charged surface. Its thromboresistant properties on coated connectors are tested here and compared with uncoated standard connectors, as well as with the Carmeda BioActive surface (CBAS) heparin surface coating. A partial cardiopulmonary bypass bovine model (body weight 68 +/- 5 kg) was selected, and the surfaces were exposed to the blood stream (pump flow 3.5 L/min) for up to 350 minutes without systemic heparinization. Thereafter, another set of samples was exposed to stagnant blood for 20 minutes. Besides hemodynamic, hematologic, and biochemical analyses, the macroscopic appearance of 45 blood exposed surface samples were graded semiquantitatively on a scale of 0 to 10: no macroscopic deposits = grade 0, one spot (1 mm diameter) = grade 1, two spots = grade 2, five or more spots = grade 5, 10% of the surface covered with clots = grade 6, 100% covered = grade 10. When exposed to blood flow, Trillium and CBAS coatings showed a statistically significant (p = 0.03) better thromboresistance (score: 0 +/- 0 for both) than uncoated connectors (score: 0.8 +/- 1.5) in this nonheparinized model. The same holds true when the connectors were exposed to stagnant blood (score: 0 +/- 0 for both coatings vs 4.3 +/- 2.8 for controls; p = 0.03). Therefore, Trillium coating exhibits significant antithrombotic properties that outperform standards for connectors used in clinical perfusion.

Animals↗