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Biomedical subjects

A Haverich

Publications and source records attributed to A Haverich.

At least 235 records · Page 13Linked to original sources

Effects of lung preservation with Euro-Collins and University of Wisconsin solutions on endothelium-dependent relaxations.

BACKGROUND: This study compares the effect of lung preservation using flush perfusion of Euro-Collins or University of Wisconsin solution on the pulmonary vascular function of endothelium-dependent and endothelium-independent relaxations. METHODS: Rings of canine intrapulmonary arteries were studied after 6 hours of cold ischemia in Euro-Collins or University of Wisconsin preservation solution. Endothelium-dependent and endothelium-independent relaxations were induced in organ chamber experiments. To also study pulmonary resistance vessels, endothelium-dependent relaxations were induced in in vitro perfused intact rabbit lungs. RESULTS: In the organ chamber experiments, a moderate but significant (p < 0.05) reduction in endothelium-dependent relaxations were found in the perfused and stored vessels. In perfused rabbit lungs, a decrease in the endothelial response occurred immediately after perfusion with Euro-Collins solution. However, a recovery and overshooting response was found after preservation with either solution and 6 hours of cold ischemia. A significant increase in the sensitivity of smooth muscle cells to nitric oxide was shown in both preparations. CONCLUSIONS: Both crystalloid perfusion fluids cause a decrease in endothelial function during the perfusion procedure. In contrast, endothelial function is well preserved during the ischemic time. University of Wisconsin solution induced a higher sensitivity of the vascular smooth muscle to the endothelium-derived relaxing factor nitric oxide. A reduction in pulmonary vascular resistance after University of Wisconsin preservation may be of importance in subsequent clinical lung transplantation.

Adenosine↗

Off-bypass coronary bypass grafting via minithoracotomy using mechanical epicardial stabilization.

BACKGROUND: Minimally or less invasive surgical coronary revascularization has gained increasing interest along with new techniques and devices designed for easier and safer procedures. Until recently, it appeared questionable whether grafting techniques with avoidance of cardiopulmonary bypass techniques would allow adequate results compared with conventional techniques using cardioplegic arrest. METHODS: Since June 1996, minimally invasive direct coronary artery bypass grafting procedures without cardiopulmonary bypass were intended in 24 patients (19 male, 5 female; age, 60.5 +/- 10.5 years) applying a special system (CardioThoracic Systems, Inc) for internal mammary artery access and epicardial surface stabilization approaching through an anterolateral minithoracotomy. Neither video-assisted preparation nor additional pharmacologic stabilization was applied. Concomitant risk factors and associated comorbidity were frequent. RESULTS: The procedure was completed in 23 patients, grafting the left anterior descending coronary artery (n = 21) or diagonal branches (n = 3, 1 sequential) as scheduled. In 1 case with internal mammary artery dissection, cardiopulmonary bypass and sternotomy became necessary. Simultaneous carotid endarterectomy was performed in 1 patient. There were two episodes of intraoperative ventricular fibrillation; no other major complications occurred. Postoperative evaluation was obtained in 16 patients (15 by angiography, 1 by Doppler echocardiography) so far and revealed adequate graft function and patency. CONCLUSIONS: Using specially designed instruments for internal mammary artery access and epicardial surface stabilization, minimally invasive direct coronary artery bypass grafting procedures via a minithoracotomy avoiding cardiopulmonary bypass techniques may be applied safely and successfully, even in increased risk constellations.

Cardiopulmonary Bypass↗

Status of patients presently living 9 to 13 years after orthotopic heart transplantation.

BACKGROUND: Heart transplantation has a dramatic impact on both life expectancy and quality of life in patients with terminal heart failure. The aim of the study was to evaluate psychologic, social, occupational, and somatic status of patients living long-term, 9 to 13 years after orthotopic heart transplantation. PATIENTS AND METHODS: Seventy-seven of 182 patients who received transplants between July 1983 and January 1988 in Hannover (1983-1985; n = 69 patients) and Berlin (1986-1988; n = 113 patients) have survived up to now, 9 to 13 years after transplantation (mean, 10 years 4 months). The patients and their medical records (eg, cardiac catheter studies, echocardiography) were examined to assess their somatic status. Psychologic, social, and occupational status and quality of life data were assessed by combination of self-rating questionnaires (the Short Form Health Survey Questionnaire, Giessener Beschwerdebogen [the Giessen Subjective Complaints List], the Sickness Impact Profile, and the Hospital Anxiety and Depression Scale) and semistructured interviews. RESULTS: Ninety-one percent of the patients were in New York Heart Association functional class I (70%) or II (21%). The results of the psychologic investigation revealed a definite impact of the side effects of chronic immunosuppression; however, overall, the quality of life rating was within the normal range. Sixty-seven (86%) patients were married, 51 (66%) patients were retired, 17 (22%) worked full-time or part-time, and 9 (12%) were housewife or houseman. Four male patients have fathered five healthy children 1 to 10 years after the transplantation. More than 75% of the patients had normal systolic ventricular function (mean left ventricular ejection fraction, 0.63). Coronary angiograms were normal or with minor wall irregularities in 86% (n = 66 patients), and revealed severe obstructions in 14% (n = 11). Normal function of all valves was found in one-third of the patients, tricuspid valve incompetence was not found or was insignificant in 87% (n = 67 patients) and severe in 8% (n = 10). Six patients had undergone tricuspid valve replacement, invariably for structural valve defects attributable to biopsy injuries. Fifty-eight patients (75%) exhibited various degrees of compensated renal insufficiency, 7 of them were on chronic hemodialysis, and 2 patients have undergone kidney transplantation. Hepatic function was normal in 68% (n = 52) of the patients, and 1 patient has developed liver cirrhosis. Osteoporosis was diagnosed of the discrete form in 7 (9%) and of a significant degree in 24 patients (31%); 38.5% (n = 30) complained of symptoms of polyneuropathy. CONCLUSIONS: The patients surviving 9 to 13 years after orthotopic heart transplantation are mostly in good physical status, the quality of life is comparable to the general population, and only a few of them have significantly limited in their life style. They do show the substantial chronic side effects of long-term immunosuppression, remaining treatment-dependent for a lifetime.

Adolescent↗

Influence of bicaval anastomoses on late occurrence of atrial arrhythmia after heart transplantation.

BACKGROUND: The standard technique for orthotopic heart transplantation includes right and left atrial anastomoses, which potentially disturb the integrity of the donor atria. Consequently, electrophysiologic abnormalities such as atrial flutter and fibrillation may occur even late after heart transplanation. METHODS: Over a 3-year period, 39 heart transplantations were performed using a standard right atrial anastomosis (group A), and 40 were done using bicaval anastomoses (group B). In each group, data of 30 consecutive patients with a minimum follow-up of 9 months were reviewed retrospectively to assess the incidence of atrial arrhythmia after hospital discharge. RESULTS: Early postoperatively, there was no difference in the duration of temporary pacemaker requirement and incidence of permanent pacemaker implantation (group A, 7%; group B, 7%; not significant) between the two groups. In 12 patients in group A (40%), 16 episodes of atrial flutter and fibrillation were detected 20 to 205 days after heart transplantation. In group B, 1 patient (4%) suffered from atrial fibrillation on day 116 after the operation (p < 0.001). CONCLUSIONS: Preservation of the integrity of the right donor atrium by construction of bicaval anastomoses results in a significantly decreased incidence of atrial flutter and fibrillation after heart transplantation when compared with the standard technique.

Adult↗

Anti-rejection prophylaxis by blocking selectin dependent cell adhesion after rat allogeneic and xenogeneic lung transplantation.

OBJECTIVE: Adhesion molecules regulate the infiltration of leukocytes into the graft during rejection after lung transplantation. The first step of the adhesion cascade is mediated by selectins. Sialyl-LewisX is a ligand of P-selectin. The purpose of the study was to evaluate SLX, a synthetic oligosaccharide analog of Sialyl-LewisX, for anti-rejection prophylaxis after allogeneic and xenogeneic left lateral, orthotopic rat lung transplantation. METHODS: In groups A and B, allogeneic lung transplantation was performed using fully incompatible rat strains (donors: Dark-Agouti (RT1a); recipients: Lewis (RT11)). In group A (n = 10), recipients recieved 200 microg/d SLX i.v. on day 0-4. Group B rats (n = 10) served as untreated controls. The animals were sacrificed on days 5 and 10, respectively. In groups C and D, xenogenic lung transplantation was performed using Gold Syrian hamsters as donors and Lewis rats as recipients. In group C (n = 10), recipients received 200 microg/d SLX i.v. on day 0-4. Group D rats (n = 10) served as untreated controls. The animals were sacrificed on days 2 and 5, respectively. Rejection was graded by histology from 0 (no rejection) to 5 (necrosis). By immunhistology, alveolar, interstitial CD11a, CD18 and VLA-4 positive leukocytes were counted. RESULTS: Histologically, there were a lower grade of rejection (A: 2.7 +/- 0.6; B: 4.0 +/- 0.0; P < 0.05) and fewer CD11a positive leukocytes (A: 66 +/- 27; B: 186 +/- 73; P < 0.05) on day 5 in the SLX-treated allograft group compared to the untreated group. In xenotransplantation, SLX also reduced the grade of rejection (C: 3.3 +/- 0.5; D: 4.7 +/- 0.5; P < 0.05) and the number of CD11a positive leukocytes (C: 145 +/- 22; D: 176 +/- 20; P < 0.05) on day 2. CONCLUSIONS: It is concluded, that the administration of SLX significantly reduces allograft rejection. After discontinuation treatment with SLX unmodified rejection appeared. SLX also modifies xenograft rejection, but to a lesser extent, and xenograft necrosis appeared during treatment in this model.

Animals↗

Ischemic preconditioning prior to myocardial protection with cold blood cardioplegia in coronary surgery.

OBJECTIVE: Encouraging results on myocardial preconditioning in experimental models of infarction, stunning or prolonged ischemia raise the question whether preconditioning techniques may enhance conventional cardioplegic protection used for routine coronary surgery. METHODS: A prospective clinical trial was conducted to investigate the effect of additional ischemic normothermic preconditioning prior to cardioplegic arrest applying cold blood cardioplegia in patients scheduled for routine coronary surgery (3 vessel disease, left ventricular ejection fraction > 50%). Two cross clamp periods of 5 min with the hearts beating in sinus rhythm were applied followed by 10 min of reperfusion, each (n = 7, group I). Inducing moderate hypothermia cold blood cardioplegia was delivered antegradely. In control groups, cold intermittent blood cardioplegia (n = 7, group II) was used alone. Coronary sinus effluents were analyzed for release of creatine kinase (CK), CK-MB, lactate, and troponin T at 1, 3, 6, 9, and 12 h. In addition, postoperative catecholamine requirements were monitored. RESULTS: The procedure was tolerated well, and no perioperative myocardial infarction in any of the groups studied occurred. Concentrations of lactate tended to be higher in group I, but this difference was not significant. In addition, no significant differences for concentrations of CK, CK-MB, and troponin T were found. Following ischemic preconditioning an increased dosage of dopamine was required within the first 12 h postoperatively (group I: 2.63 +/- 1.44 microg/kg/min, group II: 0.89 +/- 1.06 microg/kg/min). CONCLUSIONS: Combining ischemic preconditioning and cardioplegic protection with cold blood cardioplegia does not appear to ameliorate myocardial protection when compared to cardioplegic protection applying cold blood cardioplegia alone. Inversely, contractile function seemed to be impaired when applying this protocol of ischemic preconditioning.

Biomarkers↗

Detection of diastolic dysfunction: acoustic quantification (AQ) in comparison to Doppler echocardiography.

OBJECTIVES: To evaluate the potential of acoustic quantification (AQ) in detection of diastolic dysfunction in comparison to Doppler analysis, we investigated, as a model of restrictive filling pattern, nonrejecting heart transplant recipients early postoperatively. BACKGROUND: AQ, an ultrasonic backscatter imaging system, enables instantaneous calculation of cavity areas and thus provides a new approach to diastolic function. METHODS: Of 27 pts who have undergone heart transplantation, echocardiography has been performed at the day of biopsy. During a time course of 8 weeks echocardiographic data have been analysed at 3 different time points (early, mid and late) in 16 nonrejecting pts. Indexes of the area-change waveform and its 1. derivative (dA/dt) obtained by AQ were opposed to usual Doppler indexes. RESULTS: In comparing data of the early and late time point of investigation, significant changes of early diastolic filling were detectable by AQ as well as by Doppler: End-diastolic areas have increased (p < 0.001), while peak filling rate (p < 0.0001), slope of area change during rapid filling (p < 0.001) and amount of relative area change during rapid filling (p < 0.001) have decreased. Complementary, Doppler derived pressure half-time (p < 0.0001) and isovolumic relaxation time (p < 0.0001) have increased while the peak early filling velocity (p < 0.0001) and its time velocity integral (p < 0.001) have decreased. CONCLUSION: An initial restrictive filling pattern has improved 8 weeks postoperatively. Since multiple indexes, obtained from the area change waveforms, in particular the for end-diastolic area normalized peak filling rate, seem to be highly sensitive in detecting changes of diastolic function, AQ may play an important complementary role in non-invasive evaluation of restrictive filling pattern.

Adult↗

Effect of oligosaccharides on rejection and reperfusion injury after lung transplantation.

BACKGROUND: During rejection and reperfusion injury, infiltration of leukocytes into the lung allograft is regulated by adhesion molecules, especially selectins. Sialyl-Lewis X (SLX), an oligosaccharide, is a membrane ligand molecule of P-selectin adhesion receptors. In this study, we investigated the effect of intravenous administration of a synthetic oligosaccharide analog of SLX on rejection and reperfusion injury after rat lung transplantation. METHODS: Left lateral, orthotopic, allogeneic lung transplantation was performed between fully incompatible rat strains (Dark Agouti-->Lewis) after an average total ischemic time of 45 minutes. Group A (n = 6) served as control; no immunosuppression was used. In group B (n = 6), rats received 200 micrograms/kg/day SLX intravenously on days 0 to 4. The animals were killed on days 5 and 10, respectively. In groups C and D, syngeneic lung transplantation was performed (Lewis-->Lewis), with an ischemic time of 7 hours. Group C (n = 6) served as untreated controls. Group D rats (n = 6) received a single dose of 20 mg/kg SLX at the end of the ischemic time. The animals were killed on days 2 and 5, respectively. RESULTS: In group B rats, treated for rejection, a lower grade of rejection (2.7 +/- 0.6 vs 4.0 +/- 0.0, p < 0.05) and fewer infiltrating CD11a-positive leukocytes (6.6 +/- 2.7 vs 18.6 +/- 7.3, p < 0.05) were found histologically compared with group A. In group D rats, treated for reperfusion injury, a significant reduction of reperfusion injury was detected on chest radiograms and by histologic study. CONCLUSIONS: A synthetic oligosaccharide analog of SLX reduces allograft rejection and reperfusion injury by abrogation of P-selectin-dependent leukocyte-endothelial interaction. According to these findings, treatment with oligosaccharides to reduce reperfusion injury and rejection seems to be a promising strategy for clinical lung transplantation.

Animals↗

[Minimal invasive bypass operations on the beating heart and using mechanical stabilization of the heart surface].

Different minimally invasive techniques are currently being controversially discussed among cardiac surgeons. For revascularization of anterior myocardial vessels, off-bypass procedures were performed in 64 cases through an anterolateral submammary minithoracotomy using the left internal mammary artery. Application of mechanical epicardial stabilization facilitated adequate exposure of the anastomosis and resulted in good patency rates and a low number of complications.

Aged↗

[Wound infections after heart surgery interventions--a cost analysis].

Decreasing financial resources in the health care system require effective cost management. For this reason and due to special modalities of reimbursement regulations for open heart procedures, we analyzed the extent of additional costs caused by subsequent deep wound infections requiring surgical revision. The real costs of 12 consecutive cases of sternal infections out of a total of 1,124 open heart procedures in 1996 were assessed and differentiated.

Cardiac Surgical Procedures↗

Ischemic preconditioning enhances donor heart preservation.

Ischemic preconditioning has not been assessed in an experimental model for myocardial preservation during heart transplantation. Using isolated working rat hearts, ischemic preconditioning was investigated as an adjunct to isolated hypothermic (group 1), crystalloid (group 2: University of Wisconsin solution; group 3: St. Thomas' Hospital cardioplegic solution II; group 4: Bretschneiders' cardioplegic solution), and noncrystalloid (group 5: cold blood cardioplegia) preservation during a 10-hr period of global ischemia at 4 degrees C. After acquisition of functional baseline data, ischemic preconditioning was induced with one cycle of 5 min of normothermic ischemia and 5 min of reperfusion before induction of global hypothermic ischemia (n= 10/group). Nonpreconditioned hearts (n= 10/group) were assessed for control. Ischemic preconditioning improved postischemic: functional recovery. Thus, aortic flow after 60 min of reperfusion recovered to 0%, 8%, 0%, 1% and 0% in control groups 1 to 5 without ischemic preconditioning and 21%, 25%, 10%, 8%, and 3% in groups 1 to 5 with ischemic preconditioning. The same pattern of recovery was observed in regard to postischemic maximum developed left ventricular pressure, which recovered to 21%, 56%, 30%, 36%, and 19% in groups 1 to 5 without preconditioning and 46%, 75%, 49%, 40%, and 47% in the corresponding groups with ischemic preconditioning. High-energy phosphate contents were not significantly different between preconditioned hearts and corresponding nonpreconditioned control hearts. Creatine kinase leakage during early reperfusion was found to be reduced with ischemic preconditioning. Thus, we have demonstrated that ischemic preconditioning can improve contractile function after global hypothermic ischemia in the isolated rat heart and we have shown that this protection is additive to that of hypothermia-induced protection during global ischemia at 4 degrees C. This endogenous mechanism of cardioprotection was effective regardless of whether preservation was accomplished using cardioplegic solution or topical hypothermia alone. This may have clinical implications in myocardial preservation for heart transplantation.

Adenosine↗

Enhancement of cytomegalovirus infection and acute rejection after allogeneic lung transplantation in the rat.

A possible mechanism of the induction of lung transplant rejection by cytomegalovirus (CMV) infection is the inflammatory upregulation of adhesion ligand molecules on transplant endothelia by the viral infection leading to leukocyte activation. To study this question a rat model of rat cytomegalovirus (RCMV) infection and acute lung transplant rejection was established to study: (1) the influence of RCMV infection on the course of rejection, (2) the influence of rejection on the course of RCMV infection, and (3) the influence of RCMV on adhesion molecule expression and leukocyte infiltration. For this Lew (RT1l) rats received either syngenic (n=25) or allogeneic (BN, RT1n; n=38) left lateral lung transplants. Postoperatively, CsA 25mg/kg was given on days 1-3 and triple drug (CsA, Aza, Pred) immunosuppression was given from days 4-10 to induce systemic RCMV infection and acute rejection developed from postoperative day (POD) 15-25 in allogeneic transplants. In RCMV-positive animals the rejection grade was gradually increased at POD 15 and 18. Furthermore, after allogeneic transplantation an enhanced viral infection of the lung transplant as early as POD 11 was found and increased salivary gland PFU titers on days 20 and 25. In the absence of rejection infiltration a maximal induction of ICAM-1 adhesion molecules was found on lung endothelia in RCMV+ allogeneic animals as compared with noninfected controls. This induction was found to lesser degree for VCAM-1 and MHC class II adhesion ligand molecules. This was accompanied by a significantly increased CD11a+ and CD49d+ leukocyte infiltration into the alveolar interstitium on day 11 and 15 in infected transplants. The results show an enhancement of RCMV infection after allogeneic lung transplantation leading to endothelial activation and recruitment of CD11a/CD49d+ leukocytes. This mechanism may strongly influence transplant inflammation and the long-term course of lung transplant rejection.

Animals↗

Therapy for lung failure using nitric oxide inhalation and surfactant replacement.

Nitric oxide inhalation and surfactant replacement therapy are relatively new concepts in the treatment of respiratory failure due to hypoxia and reperfusion injury after lung transplantation. We report on a patient in whom reperfusion injury of the lung developed after resuscitation and implantation of a biventricular assist device for sudden cardiac arrest. Lung failure developed within 12 hours after implantation of the biventricular assist device. Lung function was reestablished using combined therapy of nitric oxide and surfactant. Heart transplantation was performed successfully thereafter. This case indicates the potential role of a combined therapy of nitric oxide and surfactant in acute hypoxic lung failure.

Adult↗

Systemic inflammatory response syndrome after cardiac operations.

BACKGROUND: A systemic inflammatory response after open heart operation may be responsible for hyperdynamic circulatory instability and organ dysfunction. To what extent mediator release is involved needs to be clarified. METHODS: Ten patients with postoperative hyperdynamic circulatory dysregulation (group I) requiring application of alpha-constrictors and 10 patients with routine cardiac procedures and stable postoperative hemodynamic indices (group II) were analyzed for mediator release and metabolic and hemodynamic changes until the third postoperative day. RESULTS: Group I patients showed a significantly increased cardiac index and decreased systemic vascular resistance after bypass (cardiac index, group I: 5.2 +/- 1.2 L.min-1.m-2, group II: 2.5 +/- 1.6 L.min-1.m-2; systemic vascular resistance, group I: 495 +/- 204 dyne.s. cm-5, group II: 1,356 +/- 466 dyne.s.cm-5) and at 3 hours (cardiac index, group I: 4.4 +/- 0.8 L.min-1.m-2, group II: 2.9 +/- 0.6 L.min-1.m-2; systemic vascular resistance, group I: 567 +/- 211 dyne.s.cm-5, group II: 1,053 +/- 273 dyne.s.cm-5). Significantly higher serum levels of interleukin-6 were assessed in group I (postbypass, group I: 6,812 +/- 9,293 pg/mL, group II: 295 +/- 303 pg/mL; 3 hours, group I: 3,474 +/- 5,594 pg/mL, group II: 286 +/- 296 pg/mL). Concentrations of elastase, tumor necrosis factor, soluble tumor necrosis factor receptor, and interleukin-8 were elevated in group I (not significant). Early postoperative levels of soluble E-selectin and soluble intercellular adhesion molecule were also higher in group I (not significant). Continuously increased levels of endotoxin could be detected in only 3 of 10 patients in group I. Severe lactic acidosis (> or = 5 mmol/L) occurred in group I only. CONCLUSIONS: Postoperative hyperdynamic instability after open heart operations appears to be associated with a certain pattern of mediator release. In particular, interleukin-6 appears to be involved in circulatory dysregulation and metabolic derangement.

Acidosis, Lactic↗

Adverse effects of crystalloid cardioplegia and slow cooling for protection of immature rat hearts.

BACKGROUND: Studies on the benefit of methods for protection of the hypertrophied immature myocardium are rare and controversial. METHODS: We assessed the effects of (1) rapid cooling by topical hypothermia alone, (2) slow prearrest cooling by coronary perfusion hypothermia, and (3) cardioplegic cardiac arrest with St. Thomas' Hospital solution no. 2 for protection of isolated immature rat hearts (age, 28 days) during 8 hours of global ischemia at 10 degrees C. Myocardial hypertrophy was induced noninvasively by lifelong feeding of a low iron diet. Recovery of left ventricular function, metabolism, and myocardial fine structure were assessed. RESULTS: In hypertrophied hearts, protection by topical hypothermia alone resulted in significantly improved postischemic recoveries of maximum left ventricular pressure and rate of pressure rise compared with the method of slow cooling or application of cardioplegia (40.6% +/- 5.0% and 38.1% +/- 5.9%, mean +/- standard error of the mean; p < 0.05). The same pattern of recovery was observed among nonhypertrophied control hearts. Regardless of the method of protection, hypertrophied hearts revealed a significantly larger interstitial space at the end of reperfusion than control hearts. In hypertrophied hearts, postischemic adenosine triphosphate concentrations were higher with topical hypothermia alone for protection than with the other methods. CONCLUSIONS: Rapid cooling by topical hypothermia alone provides superior protection of hypertrophied immature rat hearts as compared with slow prearrest cooling. Application of St. Thomas' Hospital cardioplegic solution no. 2 does not improve protection and even hinders postischemic functional recovery.

Adenosine Triphosphate↗