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Biomedical subjects

R Hetzer

Publications and source records attributed to R Hetzer.

At least 19 recordsLinked to original sources
PubMed1999

Identification and expression of delta-isoforms of the multifunctional Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human myocardium.

Despite its importance for the regulation of heart function, little is known about the isoform expression of the multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII) in human myocardium. In this study, we investigated the spectrum of CaMKII isoforms delta2, delta3, delta4, delta8, and delta9 in human striated muscle tissue. Isoform delta3 is characteristically expressed in cardiac muscle. In skeletal muscle, specific expression of a new isoform termed delta11 is demonstrated. Complete sequencing of human delta2 cDNA, representing all common features of the investigated CaMKII subclass, revealed its high homology to the corresponding rat cDNA. Comparative semiquantitative reverse transcription-polymerase chain reaction analyses from left ventricular tissues of normal hearts and from patients suffering from dilated cardiomyopathy showed a significant increase in transcript levels of isoform delta3 relative to the expression of glyceraldehyde-3-phosphate dehydrogenase in diseased hearts (101. 6+/-11.0% versus 64.9+/-9.9% in the nonfailing group; P<0.05, n=6). Transcript levels of the other investigated cardiac CaMKII isoforms remained unchanged. At the protein level, by using a subclass-specific antibody, we observed a similar increase of a delta-CaMKII-specific signal (7.2+/-1.0 versus 3.8+/-0.7 optical density units in the nonfailing group; P<0.05, n=4 through 6). The diseased state of the failing hearts was confirmed by a significant increase in transcript levels for atrial natriuretic peptide (292. 9+/-76.4% versus 40.1+/-3.2% in the nonfailing group; P<0.05, n=3 through 6). Our data characterize for the first time the delta-CaMKII isoform expression pattern in human hearts and demonstrate changes in this expression pattern in heart failure.

Adult↗
PubMed1999

Myocardial adenine nucleotides, glycogen, and Na, K-ATPase in patients with idiopathic dilated cardiomyopathy requiring mechanical circulatory support.

Acute decompensation leading to progressive pump failure is a main cause of death in patients with congestive heart failure. To find possible metabolic defects associated with the onset of this fatal occurrence, we measured myocardial adenine nucleotides, glycogen, and Na,K-ATPase in patients with end-stage idiopathic dilated cardiomyopathy. The biopsy specimens were obtained from the right ventricle of beating hearts during implantation of a biventricular assistance device in 23 patients (group I) suffering from irreversible cardiogenic shock and during heart transplantation in 20 patients (group II) in compensated heart failure. Left ventricular ejection fraction (LVEF) was determined preoperatively by echocardiography. Left ventricular function in group I was more severely impaired than in group II (LVEF 16.8%+/-4.6% vs 22.1%+/-5.1 %; p <0.01). Myocardial adenosine triphosphate (ATP) in group I was significantly reduced in comparison with group II (119.4+/-10.2 vs 27.7+/-7.4 nmol/mg noncollagen protein; p <0.01). There was no difference in glycogen levels. Na,K-ATPase concentration in group I (n = 8) was lower than that of group II (n = 20) (425+/-80 vs 498+/-75 pmol/g wet weight; p <0.05). Linear regression analyses showed a significant correlation between adenosine triphosphate (ATP) and LVEF (r = 0.41, p <0.01) and between Na,K-ATPase and LVEF (r = 0.55, p <0.01). These results indicate that loss of myocardial ATP and Na,K-ATPase could partially contribute to the development of spontaneous deterioration of the chronically overloaded heart.

Adenine Nucleotides↗
PubMed1999

Successful total correction of complete atrioventricular canal, total anomalous pulmonary venous drainage and unroofed coronary sinus in an infant.

An infant with complete atrioventricular canal, total anomalous pulmonary venous drainage into the left superior vena cava and an unroofed coronary sinus successfully underwent total correction. A homograft vein was used to connect the proximal left superior vena cava to the right atrium and can be recommended when other methods of correction of unroofed coronary sinus cannot be used.

Anastomosis, Surgical↗
PubMed1998

Screening the human bradykinin B2 receptor gene in patients with cardiovascular diseases: identification of a functional mutation in the promoter and a new coding variant (T21M).

To elucidate if genetic variants in the bradykinin B2 receptor (B2) gene occur that could affect receptor expression and function, we screened for mutations in the promoter and in the coding region of the human B2 gene. In our initial study we analyzed 92 consecutive, unrelated subjects (including 25 patients with hypertrophic cardiomyopathy, 18 patients with dilated cardiomyopathy (DCM), 25 patients with hypertension, 18 patients with coronary heart disease, and 6 patients with valvular heart disease) using nonradioactive polymerase chain reaction-single-strand conformation polymorphism analysis as mutation screening method. We detected eight as yet unknown polymorphic sites in the promoter region of the B2 gene (-845 C/T, -704 C/T, -649 insG, -640 T/C, -536 C/T, -412 C/G, -143 C/T and -78 C/T) with allele frequencies between 0.5 and 13%. One of them (-412 C/G) destroys a Sp1 binding site and abolishes protein binding to this Sp1 site in human umbilical vein endothelial cells and human vascular smooth muscle cells. In the protein-coding region one new coding variant (T21M) with the potential to create a truncated receptor isoform was detected. We determined the frequency of the promoter variant at position -412 (C --> G) and the newly identified coding variant (T21M) in extended samples of 69 patients with HCM, 163 patients with DCM, 109 patients with hypertension, and 173 healthy anonymous blood donors. The promoter variant (-412 C/G) was found in one blood donor and the T21M mutation was not found in the control population. Therefore, it appears that these mutations are rare events and the determination of clinical significance will be a demanding task in the future.

Cardiovascular Diseases↗
PubMed1998

[Electron-beam computed tomography in heart surgery].

PURPOSE: Electron beam CT (EBCT) has been devised to improve the imaging of the heart and the great vessels. Therefore, this method is expected to facilitate the imaging workup of patients referred for cardiothoracic surgery. We set out to review the most important surgical issues that can be addressed with this method. METHODS: From June, 1997 until July, 1998, more than 300 patients were referred from cardiothoracic surgery. In a retrospective analysis, diagnostic results were reviewed and compared with surgical findings and the clinical course. RESULTS: Aortocoronary bypass graft occlusions were detected with a sensitivity of 100% and a specificity of 95%. Calcifications of the aorta, pericardium and intracardiac tumors were surgically confirmed in all instances. There was a significant association of the degree of coronary artery calcification and the progression of cardiac allograft vasculopathy in 50 heart transplant recipients. In EBCT of the aorta, a high degree of diagnostic confidence was found for aortic dissection, aortic wall hematoma or aortic perforation. CONCLUSIONS: We conclude that EBCT represents an important diagnostic tool both for surgical planning and postoperative surveillance in cardiothoracic surgery.

Adult↗
PubMed1998

Soluble L-selectin plasma concentrations in infants undergoing heart surgery: no association with capillary leak syndrome or need for respiratory support.

OBJECTIVE: In critical care patients at risk of developing the acute respiratory distress syndrome (ARDS), low soluble L-selectin (sCD62L) plasma concentrations have been shown to be associated with progression to ARDS and prolonged subsequent mechanical ventilation. This study aimed to determine the usefulness of sCD62L plasma concentrations to identify infants undergoing cardiovascular surgery who are at risk for postoperative pulmonary dysfunction and capillary leaks. DESIGN: Serial measurements of sCD62L plasma concentrations in a cohort of infants with congenital heart disease before, during, and after surgery for 4 consecutive days. SETTING AND PATIENTS: Infants aged 3-337 days undergoing cardiovascular surgery with (N = 27) or without (N = 12) cardiopulmonary bypass in a tertiary care center. RESULTS: sCD62L concentrations before surgery showed a strong correlation with the infant's age (r = 0.77, p < 0.001). During surgery, sCD62L levels dropped from 9.0 +/- 0.7 to 5.6 +/- 0.4 nmol/l (mean +/- SEM; p < 0.001). The minimum sCD62L concentration during and after surgery did not differ between infants operated upon with or without cardiopulmonary bypass (p > 0.1) or in infants who did (N = 10) or did not (N = 29) develop capillary leak syndrome. Whereas capillary leak syndrome was associated with prolonged mechanical ventilation (p < 0.01), there was no relationship between sCD62L concentrations at baseline or at any time thereafter and number of hours on the ventilator(p > 0.1). CONCLUSION: sCD62L concentrations before or after surgery are not apt to identify infants at increased risk of prolonged mechanical ventilation.

Age Factors↗
PubMed1998

["Cox/Maze-III operation" as surgical therapy of chronic atrial fibrillation during mitral valve and atrial septal defect II operation].

PROBLEM: Atrial fibrillation is associated with significant morbidity and mortality. The increased risk of thromboembolism makes constant anti-coagulation necessary, while the absence of atrial contraction worsens the hemodynamic situation. In this study we examined the results of simultaneous surgical treatment of chronic atrial fibrillation through "Cox/Maze-III-procedure" while mitral valve surgery and atrial septal closure. PATIENTS AND METHODS: Between February 1995 and July 1997 sixteen patients aged 50 to 72 y (mean: 59 y) underwent open heart surgery (mitral valve replacement n = 10, reconstruction n = 3; mitral valve reconstruction and atrial septal closure n = 1, atrial septal closure n = 1, thrombectomy from left atrium n = 1) and "Cox/Maze-III-procedure" in one session. Preoperative duration of chronic atrial fibrillation was between 2 and 12 y (mean: 5.0 y). The patients were examined preoperatively and postoperatively 3, 6, 12, and 24 months after surgery using the following methods: transesophageal echocardiography (TEE), ECG, long-term ECG, and stress ergometry. RESULTS: During the early postoperative period (< 7 d) all of the patients were in sinus rhythm or atrial pacing; eight patients intermittently had atrial fibrillation. In the follow-up period from 1 to 27 months (mean 14 months), 15 patients have a stable sinus rhythm (94%). One patient, preoperatively known to have intermittent tachybradycardia, received a pacemaker 2 months postoperatively for sinus bradycardia. Postoperatively in TEE patients showed left atrial contraction with improvement of hemodynamic situation. Stress ergometry 6 months postoperatively showed lower increasements of heart rate, at 12 months normal frequency. CONCLUSION: The surgical treatment of chronic atrial fibrillation through "Cox/Maze-III-procedure" can be performed combined with other heart operations without increased perioperative or postoperative risks. The Maze-procedure is an effective surgical therapy of chronic atrial fibrillation. Postoperatively there is an improvement of the hemodynamic situation because of sinus rhythm and synchrone atrioventricular contraction.

Aged↗
PubMed1998

[Measuring bioelectric myocardial impedance as a noninvasive method for diagnosis of graft rejection after heart transplantation].

12 beagle dogs underwent neck-heart transplantation and were immunosuppressed with cyclosporine and methylprednisolone. Intramyocardial impedance was determined twice daily with four screw-in electrodes in the right and left ventricle. Transmyocardial biopsies and the intra-myocardial electrogram (IMEG) were performed as reference methods. 19 rejection episodes were induced. When acute rejection was seen in histology the animals were treated with pulsed 125 mg methylprednisolone over 5 consecutive days and immunosuppression was raised to sufficient levels. Successful treatment of rejection was controlled by biopsy. All hearts showed a uniform decrease of impedance of about 28.3% +/- 5.5% immediately after implantation, then reaching a stable plateau after 7 to 8 days. Impedance values then remained unchanged as long as rejection was absent. Biopsy findings of grade 1A to 1B (ISHLT) were accompanied by a statistically significant increase of impedance of 12.2% +/- 2.5%, of grade 2 to 3A of 19.2% +/- 3.2%, and of grade 3B to 4 of 27.0% +/- 2.9%. Sensitivity was 95%, specificity 91%. Successful treatment of rejection led to a uniform decrease of impedance to intramyocardial impedance for high frequencies can reliably indicate alterations of the cell membrane and the intracellular space during acute cardiac allograft rejection. The amount of increase of impedance is a reliable noninvasive parameter to graduate acute cardiac allograft rejection. The success of treatment of rejection can also be monitored by impedance. This noninvasive method is applicable for telemetric rejection monitoring via an implantable device, which would allow continuous rejection surveillance of a patient at home without hospital admission.

Animals↗
PubMed1998

Complement and contact activation during cardiovascular operations in infants.

BACKGROUND: By comparing the results of cardiac operations with or without cardiopulmonary bypass (CPB) in infants in a prospective study, we sought to determine which part of the postoperative systemic inflammatory response was caused by CPB. METHODS: Thirty-five patients were divided into two groups: 11 infants operated on without CPB and 24 infants operated on with CPB. Blood samples were drawn before, during, and after the operation. We assessed complement function and the concentrations or activities of C1q, C3, C4, C1 inhibitor, factor B, the activated split product C3a, and prekallikrein and factor XIIa of the contact system. RESULTS: All of the patients exhibited a decrease of complement proteins. This was greater in infants who underwent CPB. A increase in C3a and factor XIIa and changes in prekallikrein activity occurred only in infants during CPB. CONCLUSIONS: Complement activation occurs in all infants, but is significantly higher in the group with CPB. Contact activation only occurs in patients who undergo CPB. Thus, the inflammatory response is caused by the use of a CPB circuit and to a lesser degree by surgical procedures and anesthesia.

Cardiac Surgical Procedures↗
PubMed1998

Coronary bypass flow during use of intraaortic balloon pumping and left ventricular assist device.

BACKGROUND: Intraaortic balloon pumping (IABP) and left ventricular assist device (LVAD) are used for left ventricular support when low cardiac output occurs after a coronary bypass operation for serious coronary artery disease. There are hemodynamic differences in blood flow in various kinds of coronary artery bypass grafts, caused by their inherent physiologic characteristics. The hemodynamic effects of left ventricular assistance with IABP and LVAD on blood flow through various coronary artery bypass grafts were investigated. METHODS: An ascending aorta-coronary bypass graft (ACB), an internal thoracic artery, and a descending aorta-coronary bypass graft were anastomosed to the left anterior descending coronary artery in a canine model. In this experimental model, the blood flow to the same coronary bed in the three types of grafts could be evaluated. Blood flow in the left anterior descending coronary artery through the three types of coronary bypass grafts was studied in this model during or in the absence of ventricular assistance. RESULTS: In the control study, the systolic blood flow did not differ among the three types of grafts, but the diastolic flow decreased in the following order: with the ACB, the internal thoracic artery, and the descending aorta-coronary bypass graft. The systolic flow during IABP and LVAD was similar to the control flows. Use of IABP increased the diastolic flow by 75.3%+/-12.4% of the control value in the ACB, 37.9%+/-25.0% in the internal thoracic artery, and 21.2%+/-11.4% in the descending aorta-coronary bypass graft. The LVAD increased the diastolic flow by 97.7%+/-18.7% of the control value in the ACB, 64.5%+/-25.7% in the internal thoracic artery, and 63.0%+/-27.9% in the descending aorta-coronary bypass graft. The diastolic blood flows in the left anterior descending coronary artery and the three types of grafts were significantly greater with IABP than the control values, and significantly greater with LVAD than with IABP and the control values. The degrees of increase of diastolic flows in the left anterior descending coronary artery and the ACB with IABP and LVAD were significantly greater than in the arterial grafts (p < 0.01). CONCLUSIONS: The diastolic flows in the internal thoracic artery and descending aorta-coronary bypass graft increased less than in the native left anterior descending coronary artery and ACB during left ventricular assistance, particularly with IABP. It is important for the selection of tactics for the management of catastrophic status after coronary bypass grafting to consider the hemodynamic characteristics of the graft.

Animals↗
PubMed1998

Daily noninvasive rejection monitoring improves long-term survival in pediatric heart transplantation.

BACKGROUND: Acute rejection episodes and transplant vasculopathy (TVP) account for most of the late deaths after heart transplantation in both adults and children. Accumulating evidence indicates that fatal acute rejection and TVP are related to unrecognized and untreated early and ongoing acute rejection. Day-by-day surveillance of the heart and prompt treatment of any rejection may yield improved long-term survival. METHODS: In almost all patients having transplantation at our institution (978 patients since 1986), the intramyocardial electrogram (IMEG) was recorded routinely every day through a telemetry pacemaker and transmitted to our center by telephone modem. Earlier studies showed a substantial voltage drop in the IMEG QRS complex is highly indicative of acute rejection, including humoral rejection. In this study, we reviewed the data from 69 pediatric patients up to 16 years old for the incidence of acute rejection, TVP, and long-term outcome. Diagnostic endomyocardial biopsies were performed in only 10 patients, and recent coronary angiograms from 29 children were reviewed. RESULTS: In 50 children discharged after heart transplantation, IMEG surveillance data for a mean of 2.9 years indicated 72 acute rejection episodes. During follow-up of 1 month to 10.5 years (mean follow-up, 4.4 years), 2 patients died late of causes unrelated to either rejection or TVP. Another patient died of rejection during unrecognized underimmunosuppression nearly 8 years after transplantation and nearly 31/2 years after discontinuing IMEG recordings. Two patients without IMEG recording died of acute rejection or late TVP. In 1 patient, moderate TVP was seen on an angiogram after 41/2 years (incidence, 2.0%; 5-year incidence, 5.6%). CONCLUSIONS: Daily recording of the IMEG can reliably detect early stages of acute rejection episodes, and immediate rejection treatment seems to keep the incidence of TVP low. The IMEG appears better than all the other rejection monitoring protocols currently in use.

Acute Disease↗
PubMed1998

Circulatory support with pneumatic paracorporeal ventricular assist device in infants and children.

BACKGROUND: Mechanical circulatory support in intractable heart failure in children has been limited to centrifugal pumps and extracorporeal membrane oxygenation: Since 1990 small adult-size pulsatile air-driven ventricular assist devices "Berlin Heart" (VAD) and, since 1992 miniaturized pediatric VAD (12, 15, 25, 30 mL pumps), have been used in our institution. Since 1994 the blood-contacting surfaces of the device system have been heparin-coated. In this report the experiences with VAD support in 28 children are presented. METHODS: In 28 children-ages between 6 days and 16 years-the Berlin Heart VAD has been applied for periods of between 12 hours and 98 days (mean, 16.9 days) aiming at keeping the patient alive and allowing for recovery from shock sequelae until later transplantation or myocardial recovery. There were three groups. Group I: with primary intention of "bridge-to-transplantation" in various forms of cardiomyopathy (n = 13) or chronic stages of congenital heart disease (n = 5). Group II: "Rescue" in intractable heart failure early after corrective surgery for congenital heart disease (n = 4) or in early graft failure after a heart transplantation (n = 1). Group III: "Acute myocarditis" (n = 5) aiming at either myocardial recovery or transplantation. Twelve were brought to the operating room under cardiac massage and 25 had been on the respirator for more than 24 hours. RESULTS: Twelve patients died on the system from sequelae of profound shock-multiorgan failure, sepsis, loss of peripheral circulatory resistance-or from hemorrhagic complications (n = 4) or brain death (n = 1). Thirteen patients (groups I and III) were transplanted after support periods of between 3 and 98 days with 7 long-term survivors living now up to 7.5 years (mean, 4.4 years). Three patients (groups II and III) were weaned from the system with two long-term survivors (both in group III). There were no patients in group II who survived and the "rescue" indication has been discarded for VAD since 1992. Such patients are since treated by extracorporeal membrane oxygenation (ECMO) in our institution. Out of the 8 patients placed on VAD during 1996 and 1997, 7 were successfully supported until transplantation or weaning. Thirteen patients were extubated and mobilized on the system. Whereas with the earlier systems thrombi in the blood pumps were seen in 15 instances and 2 patients suffered from thromboembolic complications, no thrombotic events occurred with the heparin-coated systems. CONCLUSIONS: After accumulating clinical experience and several technical improvements since 1990 the use of the pediatric Berlin Heart VAD has matured into a reliable and safe system to keep patients with otherwise intractable heart failure alive until complete myocardial recovery is reached or transplantation becomes feasible. Whereas heart failure early after cardiac operation is now primarily treated by ECMO, acute myocarditis appears to be a promising precondition for complete cardiac recovery during VAD support.

Adolescent↗
PubMed1998

A modified repair technique for tricuspid incompetence in Ebstein's anomaly.

OBJECTIVE: A modified technique for tricuspid valve repair in Ebstein's anomaly restructures the valve mechanism at the level of the true tricuspid anulus by using the most mobile leaflet for valve closure without plication of the atrialized chamber. Midterm results of this therapeutic approach for patients with Ebstein's anomaly and tricuspid valve incompetence are reported. METHODS: Between October 1988 and April 1997, the incompetent tricuspid valve was repaired with our technique in 19 patients (12 female, 7 male; 2 to 54 years, mean 21 years). The indication for operation was congestive heart failure of various degrees in all patients. Tricuspid incompetence was grade II in two patients, grade III in 14, and grade IV in three. Associated congenital malformations were simultaneously repaired (interatrial communication in 18, ventricular septal defect in two, pulmonary stenosis in two, mitral valve prolapse in one). Follow-up ranged between 10 and 103 months (median 28 months) and was complete for all patients. RESULTS: There were no operative deaths. One patient with active endocarditis and pulmonary abscess died 2 months after the operation of recurrent sepsis; there were no late deaths. During follow-up, New York Heart Association functional class improved from 2.8 before the operation to 1.9 without recurrent cyanosis, and tricuspid incompetence decreased from a mean grade of 3.1 to one of 0.9, without any echocardiographic deterioration of the tricuspid valve function or right ventricular dilation. CONCLUSIONS: Our technique allows tricuspid valve repair in patients with Ebstein's anomaly, even in cases usually reserved for primary valve replacement, without late functional deterioration.

Adult↗