Christian-Friedrich Vahl

Operation for Infective Endocarditis: Results After Implantation of Mechanical Valves

BACKGROUND Operation for acute endocarditis during the active phase violates a basic surgical rule not to implant a foreign body into an infective process, resulting in a high operative mortality and the risk of early recurrent endocarditis. Several investigators analyzing risk factors for perioperative mortality and morbidity presented strategies for more favorable outcomes, but most studies suffer from the drawback of heterogeneous populations observed over a long period of time. METHODS We present a prospective study on 138 patients operated on from March 1988 to March 1996. Patients were only included if the activity of the infection was proved by positive culture of the valve leaflets or by histologic staining. During the observation period, indication for operation, surgical approach, and postoperative antibiotic therapy were standardized as much as possible. After radical debridement of all parts of infected tissue, valve replacement was carried out with mechanical prostheses. RESULTS The early mortality was 11.5% overall. High New York Heart Association functional classification, advanced age, and staphylococcal disease were significant risk factors for early mortality. The site of infection, multiple valve involvement, and prosthetic valve endocarditis did not affect the outcome. Early recurrent endocarditis was recorded in only 3 patients of the entire series. CONCLUSIONS In case of acute infective endocarditis, valve replacement with mechanical prostheses is a safe procedure, if radical operation and aggressive postoperative antibiotic therapy are performed. For further improvements of the results, earlier operation is advisable in patients with rapidly progressive cardiac deterioration and in most cases of staphylococcal endocarditis.

Intracellular calcium transient of working human myocardium of seven patients transplanted for congestive heart failure.

The afterload dependence of the intracellular calcium transient in isolated working human myocardium was analyzed in both donor and recipient hearts of seven patients undergoing transplantation because of dilated cardiomyopathy. The intracellular calcium transient (recorded by the fura 2 ratio method), force development, and muscle shortening were simultaneously recorded in small (0.6 x 4.0-mm) electrically driven (60 beats per minute) trabeculas contracting at constant preload against varying afterloads. When the fibers contracted under isometric conditions, the intracellular calcium transients of normal and failing myocardium were similar. However, in dilated cardiomyopathy, stepwise afterload reduction and the concomitant increase in shortening amplitudes were associated with extraordinary alterations in the shape of the calcium transients; the amplitude rose, the time to peak was delayed, and at minimal afterloads, a long-lasting plateau was observed, and the diastolic decay was retarded. The calcium-time integral during shortening against passive resting force was 124 +/- 5% of the isometric control in normal myocardium and 172 +/- 12% in end-stage heart failure (P < .0001). We conclude that adequate interpretation of intracellular calcium transients requires simultaneous recordings of force and shortening. The extraordinary afterload dependence of the calcium transient in end-stage heart failure may be attributed to increased dissociation of calcium from the contractile proteins, a reduced calcium reuptake rate of the sarcoplasmic reticulum, or an increased calcium inflow due to altered permeabilities of the calcium channels during shortening. A potential role of mechanosensitive calcium channels has to be considered.

Does the completeness of revascularization affect early survival after coronary artery bypass grafting in elderly patients

OBJECTIVE Usefulness and risks of incomplete versus complete revascularization are still matters of ongoing discussions. Because an increasing number of elderly patients are undergoing coronary artery bypass grafting (CABG), the question arises whether a less extensive surgical approach is more prudent than complete revascularization. METHODS Of 6531 patients undergoing isolated CABG, 859 were 75 and older at the time of operation. Mean age of the 859 patients was 77+/-2.7 years (median: 76 years); 65% were men. Follow-up enquiry by questionnaire was performed at the 180th postoperative day with a completeness of 95.6%. Assessment of the impact of incomplete revascularization utilized both multivariable analysis and propensity score matching to account for selection factors. RESULTS Incomplete revascularization was performed in 133 patients (16%). The most common reasons for incomplete revascularization were small vessels (55%) and massive calcification (32%). Mortality until 180 days after CABG was higher (n=32; 24%) after incomplete than after complete revascularization (n=105; 15%; P=0.005). By logistic multivariable regression, incomplete revascularization was identified as an independent risk factor for death (Odds ratio, 1.8; P=0.015). By time-related analysis, incomplete revascularization predominantly affected the early period after CABG (P=0.001). Aortic cross clamping time was only slightly shorter for the group with incomplete (59+/-27 min (median: 55 min) vs. 63+/-26 min (median: 58 min); P=0.1). CONCLUSIONS Incomplete revascularization increases the early risk of death after CABG in patients aged 75 years and older. The potential compensating benefit of the shorter aortic cross clamping time does not outweigh the advantages of complete revascularization. Thus, in the era of high-volume interventional approaches and minimally invasive techniques, the advantages of complete revascularization need to be considered.

Prolonged allograft survival but no tolerance induction by modulating CD28 antibody JJ319 after high-responder rat heart transplantation.

BACKGROUND Allograft rejection depends on T cell immune responses requiring antigen recognition and costimulatory signals through accessory T cell receptors, including CD28. Inhibition of CD28 signaling with a CTLA-4-immunoglobulin (Ig) fusion protein has resulted in immunosuppression and occasional T cell anergy in mouse transplant models, but not in rats. Because this approach also inhibits a potentially tolerizing signal through CTLA-4, selective blockade of CD28 ligation might induce more profound immunosuppression and transplant tolerance. METHODS The effects of escalating doses of the rat CD28 monoclonal antibody JJ319 on allograft survival were studied after vascularized heterotopic heart transplantation in a high responder strain combination (DA to Lewis). CD28 antigen modulation and circulating antibody levels were monitored by flow cytometry. RESULTS CD28 antibody JJ319 markedly prolonged cardiac graft survival compared with untreated controls (7 days, range: 6-8). A strictly dose-dependent increase in median graft survival time was demonstrated with a maximum of 36 days (range: 30-40; p <0.001) after the administration of 8 x 1 mg JJ319 i.p. (days -1 to +6 before/after transplantation). However, indefinite graft survival and tolerance could not be induced by JJ319 treatment. At the maximal dose, flow cytometry showed complete down modulation of the CD28 receptor for 10-14 days without T cell depletion in close temporal relation to antibody presence in serum. In vitro, CD28-modulated T cells showed significantly reduced responses to activation. CONCLUSIONS CD28 antibody JJ319 induces profound immunosuppression after rat heart transplantation, however without development of transplant tolerance. The underlying mechanism seems to be receptor modulation during primary alloantigen recognition. While still potentially applicable clinically, there are no qualitative or quantitative differences to the treatment with CTLA-4/lg or the blockade of CD2 or LFA-1, as reported elsewhere. Thus, a CD28-modulating approach seems not to allow therapeutic exploitation of a tolerizing signal delivered by CTLA-4 but may still be clinically applicable, especially in combined immune interventions.

Human Cardiac Inwardly-Rectifying K+ Channel Kir2.1b Is Inhibited by Direct Protein Kinase C-Dependent Regulation in Human Isolated Cardiomyocytes and in an Expression System

Background—Protein kinases A (PKA) and C (PKC) are activated in ischemic preconditioning and heart failure, conditions in which patients develop arrhythmias. The native inward rectifier potassium current (IK1) plays a central role in the stabilization of the resting membrane potential and the process of arrhythmogenesis. This study investigates the functional relationship between PKC and IK1. Methods and Results—In whole-cell patch-clamp experiments with isolated human atrial cardiomyocytes, the IK1 was reduced by 41% when the nonspecific activator of PKC phorbol 12 myristate 13-acetate (PMA; 100 nmol/L) was applied. To investigate the effects of PKC on cloned channel underlying parts of the native IK1, we expressed Kir2.1b heterologously in Xenopus oocytes and measured currents with the double-electrode voltage-clamp technique. PMA decreased the current by an average of 68%, with an IC50 of 0.68 nmol/L. The inactive compound 4-&agr;-PMA was ineffective. Thymeleatoxin and 1-oleolyl-2-acetyl-sn-glycerol, 2 specific activators of PKC, produced effects similar to those of PMA. Inhibitors of PKC, ie, staurosporine and chelerytrine, could inhibit the PMA effect (1 nmol/L) significantly. After mutation of the PKC phosphorylation sites (especially S64A and T353A), PMA became ineffective. Conclusions—The human IK1 in atrial cardiomyocytes and one of its underlying ion channels, the Kir2.1b channel, is inhibited by PKC-dependent signal transduction pathways, possibly contributing to arrhythmogenesis in patients with structural heart disease in which PKC is activated.

ROPES: a semiautomated segmentation method for accelerated analysis of three-dimensional echocardiographic data

Echocardiography (cardiac ultrasound) is today the predominant technique for quantitative assessment of cardiac function and valvular heart lesions. Segmentation of cardiac structures is required to determine many important diagnostic parameters. As the heart is a moving organ, reliable information can be obtained only from three-dimensional (3-D) data over time (3-D + time = 4-D). Due to their size, the resulting four-dimensional (4-D) data sets are not reasonably accessible to simple manual segmentation methods. Automatic segmentation often yields unsatisfactory results in a clinical environment, especially for ultrasonic images. We describe a semiautomated segmentation algorithm (ROPES) that is able to greatly reduce the time necessary for user interaction and its application to extract various parameters from 4-D echocardiographic data. After searching for candidate contour points, which have to fulfill a multiscale edge criterion, the candidates are connected by minimizing a cost function to line segments that then are connected to form a closed contour. The contour is automatically checked for plausibility. If necessary, two correction methods that can also be used interactively are applied (fitting of other line segments into the contour and searching for additional candidates with a relaxed criterion). The method is validated using in vivo transesophageal echocardiographic data sets.

Modified surgical concept for fulminant pulmonary embolism.

Surgical intervention in fulminant pulmonary embolism (PE) is still associated with an overall 30% fatal outcome which increases to about 60% when cardiopulmonary resuscitation (CPR) is necessary. Despite unfavorable conditions like hemodynamic instability, failed lysis or CPR, the surgical strategy might have a certain impact on the patients outcome since 30-40% of the surgical mortality is related to persistent right heart failure and early thromboembolic recurrence. From 1/88 to 8/94 a total of 25 patients (15 females, 10 men, mean age 57 [25-78]) years underwent emergency pulmonary embolectomy with the use of the heart-lung machine. Seventeen patients were operated upon between 1988 and 1992. A standard approach by central pulmonary artery incision with extraction of adjacent pulmonary emboli using forceps, suction of Fogarty catheters was used. Six of these patients (35%) died, with four out of six operated upon under CPR. Since 1993 we have used a modified surgical strategy in eight patients. Five patients (63%) were operated on after or under CPR. In these cases, left and right pulmonary arteries were incised peripherally and all segmental arteries were desobliterated selectively using small suction devices. Thereafter the right atrium was opened and inspected. After removal of the inferior caval vein cannula all inferior body blood was taken with cardiotomy suction while both legs and the abdomen were massaged centripetally to mobilize additional fresh thrombotic material. In three cases up to 50 cm long thrombi could be delivered. All patients have survived to date with two patients receiving a LGM caval filter placed percutaneously after bilateral postoperative phlebography had revealed ongoing thrombotic disease. We conclude that selective desobliteration of every segmental pulmonary artery in combination with simultaneous clearance of major body veins from additional thrombotic material will probably lower surgical mortality in these critically ill patients.

Downregulation of myocardial contractility via intact ventriculo-arterial coupling in the brain dead organ donor

OBJECTIVE To test the hypothesis that altered loading conditions play a key role in hemodynamic instability and cardiac dysfunction in the brain dead (BD) organ donor. METHODS BD was induced by inflation of a subdural balloon catheter. In the first part of the study, left ventricular function was assessed in a canine in situ cross-circulated heart model (n=6). Pre- and afterload and coronary perfusion pressure were kept identical in all hearts throughout the experiment. In the second part of the study, hearts (n=6) were investigated in vivo allowing the interaction between left ventricular contractility and arterial load. Left ventricular pressure--volume loops were obtained by a combined conductance-pressure catheter and the slope of the endsystolic pressure--volume relationship (Ees), arterial elastance (Ea), stroke work (SW), pressure--volume area, ventriculo--arterial coupling ratio (VAC) and mechanical efficiency (Eff) were calculated. RESULTS Induction of BD led to a hyperdynamic response in both models with a significant increase of most hemodynamic parameters. In the in situ isolated heart model, left ventricular contractility returned to baseline without any further deterioration. In contrast, in the intact circulation the hemodynamic parameters declined significantly in comparison to baseline 4 h after BD (Ees: 4.07+/-0.51 vs. 8.06+/-1.09 mmHg/ml, P<0.05, Ea: 3.17+/-0.39 vs. 4.42+/-0.30 mmHg/ml, P<0.05). However, VAC (0.78+/-0.09 vs. 0.65+/-0.14 n.s.) and Eff (73.4+/-2.1 % vs. 76.8+/-3.7 %, n.s.) remained constant over the time. CONCLUSION BD induction leads to an initial hyperdynamic reaction followed by hemodynamic instability. The facts that no cardiac dysfunction occurred if loading conditions were kept constant and the ventriculo--arterial coupling ratio and mechanical efficiency remained constant in the intact animal model indicate that decreased contractility reflects to decreased arterial elastance after brain death. Therefore, reduced contractile function after brain death at a decreased afterload may contribute to stroke work optimization.

MYOCARDIAL LENGTH-FORCE RELATIONSHIP IN END STAGE DILATED CARDIOMYOPATHY AND NORMAL HUMAN MYOCARDIUM : ANALYSIS OF INTACT AND SKINNED LEFT VENTRICULAR TRABECULAE OBTAINED DURING 11 HEART TRANSPLANTATIONS

The Frank-Starling-mechanism (FSM) was analyzed in isolated intact and skinned human left ventricular myocardium obtained from 11 heart transplantations (normal donor hearts (NDH), n=8; dilated cardiomyopathy (DCM), n=11). The new technique to utilize muscle strips from normal donor hearts which were actually implanted is described in detail.MethodsI) In electrically stimulated left ventricular trabeculae (37°C, oxygenated Krebs-Henseleit solution, supramaximal, electrical stimulation, frequency 1 Hz) force development was analyzed as a function of muscle length (NDH=8; DCM=11). II) In an additional series left ventricular myocardium was demembranized (“skinned”) by Triton-X-100. At different sarcomere lengths and calcium concentrations corresponding to pCa values of 4.3, 5.5, and 8.0 force development was measured (DCM=11; NDH=9).ResultsI) Developed force increased up to an optimum as a function of muscle length in intact NDH- and DCM-myocardium. However, the relative increment of developed force after any length step was smaller in DCM than in NDH. Near “Lmax” (muscle length associated with maximum developed force) passive resting tension was considerably elevated in DCM, indicating significantly incresed diastolic stiffness II) In skinned left ventricular DCM- and NDH-myocardium developed force depended on sarcomere length with an optimum near 2.2 μm. However, a reduction of activator calcium concentration from pCa 4.3 to pCa 5.5 produces a smaller percent decline in force at short sarcomere lengths in DCM than it does in NDH.Conclusionthe present study shows that except for diastolic stiffness and a smaller relative force increment after any, length step in DCM the Frank Starling mechanism is still present in isolated human left ventricular DCM-as in NDH-myocardium. The current study does not allow to decide whether in skinned myocardium the smaller percent decline in force after reduction of activator calcium concentrations in DCM is caused by an increased calcium sensitivity at short sarcomere lengths or decreased sensitivity at long sarcomere lengths.

Triiodothyronine reverses depressed contractile performance after excessive catecholamine stimulation

BACKGROUND Conflicting results have been reported regarding the acute effects of triiodothyronine (T3) on myocardial contractile performance. The present study analyzes the role of T3 in reversing the depressant effect of excessive catecholamine stimulation in isolated porcine left ventricular myocardium. METHODS Thirty-six left ventricular trabeculae (0.4 x 6.0 mm) obtained from 6 pigs were used for measurements of isometric force development, isotonic shortening, and intracellular calcium in three experimental series (measurement conditions: 37 degrees C; optimal length; supramaximal electrical stimulation, 1 Hz; calcium measurement, fura-2 ratio method; frequency, 225 Hz). In series 1, isometric force development was measured before and after a 60-minute incubation with 10(-7) mol/L epinephrine in preparations with (n = 6) and without (n = 6) preceding fura-2 loading for calcium measurements. In series 2, the acute effects of a 30-minute administration of T3 (10(-9) mol/L) on isometric force and intracellular calcium were analyzed (n = 6). In series 3, after simultaneous fura-2 loading and a 6-hour 10(-7) mol/L epinephrine exposure the effects of T3 (10(-9) mol/L, 30 minutes) on force development, shortening, and intracellular calcium transient were analyzed. RESULTS Long-term and high-dose epinephrine exposure induced a severe contractile depression with a significant reduction of isometric force development (p < 0.05) and increased diastolic (p < 0.001) and systolic calcium (p < 0.001). In normal porcine myocardium T3 had no effect on the extent of isometric force generation but accelerated the time course of force development (p < 0.05) and increased the calcium transient (p < 0.001). After induction of myocardial depression by epinephrine exposure T3 accelerated the intracellular calcium transients and reduced diastolic calcium. Triiodothyronine increased the shortening amplitude and the force amplitude (p < 0.01). CONCLUSIONS Triiodothyronine reverses depressed contractile performance after preceding high-dose epinephrine exposure in isolated porcine myocardium. Increased force amplitudes and unaltered or even reduced intracellular calcium transients argue in favor of a resensitization of the contractile apparatus for calcium by T3. The study supports a potential role for T3 treatment in depressed myocardium after previous excessive catecholamine exposure (eg, brain death, catecholamine treatment, ischemia).