[The use of Deep Inferior Epigastric Vessels to Revascularise Free Flaps for Reconstruction of Complex Oncosurgical Defects of the Thigh and the Abdomen]. / Epifaszial verlagerte tiefe inferiore epigastrische Gefäße als Anschlussgefäße für die mikrochirurgische Rekonstruktion komplexer onkochirurgischer Defekte des Abdomens und des Oberschenkels.

BACKGROUND: The resection of large soft-tissue sarcoma requires reconstruction with free flaps. The choice of recipient vessels is crucial for the success of surgery. PATIENTS: We report four cases with large soft-tissue sarcomas with complex anatomical relationships: two tumors of the thigh surrounding the femoral neurovascular structures and two tumors of the abdomen with infiltration of the thorax and the abdomen. All cases received multimodal interdisciplinary treatment. The anterolateral thigh (ALT) flap and the latissimus dorsi (LD) flap were employed twice for defect coverage in this series. In all cases the deep inferior epigastric (DIE) vessels were transposed to the subcutaneous compartment and used as recipient vessels. RESULTS: The mean duration of surgery was 694 ±â€…149 minutes. The mean weight of the tumor specimen was 3069 ±â€…1267 g. Three flaps healed primarily and one exhibited a minor necrosis, which was treated by excision and secondary suture. There were no cases of abdominal herniation due to the transposition of vessels. CONCLUSION: Transposition of DIE-vessels to the subcutaneus compartment is a good alternative for free flap revascularisation in this patient group. In this position, the vessels are easily accessed and used for microsurgery. This technical modification increases the reconstructive possibilities in large and previously irradiated surgical defects.

VDD-pacemaker in children--a long-term therapy?

AIMS: Transvenous AV-synchronous pacing in children started with the invention of smaller sized VDD leads and miniaturization of pacemakers. Whether or not this is a favourable long-term therapy was retrospectively investigated by us based on data from our records. METHODS: From May 1977 to July 2001 we implanted pacemakers in 104 children younger than 15 years of age. In 55 patients transvenous leads were implanted. Twelve of these (21.8 %) received a VDD pacemaker for hemodynamic reasons. RESULTS: Ages ranged from 11 months to 14.5 years (mean 7.7 +/- 4.3 y). Sizes of the children ranged from 67 to 141 cm (mean 105.9 +/- 15.5 cm) and body weight ranged from 5.3 to 62.0 kg (mean 22.5 +/- 9.8 kg). The mean follow-up period was 47.5 +/- 15.1 months. In 86.3 % of the time during follow-up pacemakers of which we obtained data were working in the VDD mode. Five of the twelve VDD patients (41.7 %) had to be reoperated because of severe traction on the leads. In all five patients the VDD systems were explanted and the patients changed to dual chamber pacemakers. The period of time between implantation and VDD lead explantation ranged from 24 to 74 months (48.6 +/- 18.5). CONCLUSIONS: VDD pacemakers can be implanted safely even in children with a low complication rate perioperatively. 41.7 % of our VDD patients had to be reoperated within the surveillance time because of severe lead tension due to thoracic growth. In our experience VDD pacemakers in smaller children seem to be a temporary solution to bridge AV-synchrony from a young age to DDD pacing in young adulthood.

[Is measuring by portable heart rate monitors (sport watches) dependable in patients with an implanted pacemaker?]. / Messen tragbare Herzfrequenz-Messgeräte (Sportuhren) bei Schrittmacherpatienten zuverlässig?

BACKGROUND AND OBJECTIVE: Regular physical exercise is advantageous for physical fitness and endurance. The intensity of exercising can be controlled by portable heart rate monitors. The aim of the study was to investigate if wearable monitors work properly in pacemaker patients. PATIENTS AND METHODS: In 30 patients with an implanted single or dual chamber pacemaker made by five different manufacturers their heart rate was determined simultaneously by surface ECG and Holter ECG, and was compared with the heart rates derived from portable heart rate monitors (Polar A1) at rest, during 6 minutes in-house walk, and while exercising at 25, 50, and 75 watts in a bicycle exercise test. The tests were done with pacing set at uni- as well as bipolar stimulation mode. RESULTS: At rest in two of 30 patients (6,6 %) paced in unipolar mode the portable heart rate monitors counted double. Under exercise conditions the portable monitors counted double in six of 26 patients (23 %) while being stimulated in unipolar mode. In bipolar stimulation mode, the portable heart rate monitors were working properly in all patients under all conditions. CONCLUSIONS: Patients with an implanted bipolar pacing system can control their physical exercising safely and accurately by means of portable heart rate monitors. Pacemaker patients who are planning regular physical exercising should be provided with an implanted bipolar pacemaker system.

Perioperative hemodynamic measurements with an implantable monitoring system (Chronicle) in a patient with severe heart failure undergoing non-cardiac surgery.

A 53-year-old male patient with severe chronic heart failure due to ischemic cardiomyopathy (LVEF 25%) awaiting heart transplantation was admitted for resection of a bladder tumor. The patient underwent implantation of a Chronicle implantable hemodynamic monitor (IHM) two years before. Thus, perioperative monitoring of heart rate, right ventricular systolic, diastolic and pulse pressure, dP/dt and estimated pulmonary artery diastolic pressure through a lead implanted in the right ventricle was performed. In the postoperative period the patient developed low-output syndrome requiring catecholamine treatment. The patient was weaned from mechanical ventilation uneventfully the same day. However, he developed symptomatic and hemodynamic worsening of heart failure shortly after reduction of inotropes and required prolonged medical treatment with catecholamines. Patients with cardiac disease are known to be at increased risk for cardiovascular complications after noncardiac surgery. Therefore, it has been suggested that such patients could potentially benefit from perioperative invasive hemodynamic monitoring. For the first time, we report a case of perioperative continuous hemodynamic monitoring with a long term-implanted device in a potential heart transplant patient.

Interference by cellular phones with permanent implanted pacemakers: an update.

AIMS: The aim of this study was to test pacemakers with feedthru filters for interference with a digital cellular telephone. METHODS: The study comprised 100 patients having their first pacemaker implantation between January 2001 and May 2003. A GSM-standard cellular phone was tested in the standby, dialing and operating mode against 23 single-chamber and 77 dual-chamber pacemakers. Continuous surface electrocardiograms, intracardiac electrograms, and marker channels were recorded when calls were made by a land phone to the cellular phone. RESULTS: In 2 patients we observed pacing inhibition with the cellular phone positioned directly above the pacemaker pocket. The unipolar and bipolar ventricular sensitivity setting was 0.25 mV in one dual-chamber pacemaker, and when we changed the sensitivity to 0.50 mV and higher no interference could be detected. The second inhibition occurred in a single-chamber pacemaker with unipolar and bipolar ventricular sensitivity setting of 0.5 mV, where a sensitivity change to 1.0 mV eliminated the interference. CONCLUSION: Anticipating a correct setting of ventricular sensitivity, currently available pacemakers equipped with feedthru filters do not show any interference with cellular phones. Since interference was only observed with sensitivity settings below 0.50 mV, we recommend that permanent programming of ventricular sensitivity should be set at 2.0 mV and higher.

Current indication for endovascular treatment of thoracic aneurysms.

The morbidity and mortality for open treatment of thoracic aortic aneurysms have declined over the years, but it is still a major clinical problem. The reason for the mortality is in almost 50% of the cases cardiac failure. Endoluminal treatment of abdominal aortic aneurysm is widely distributed and with promising results, although not as free from complications as expected 10 years ago. This technique has also been adopted for the thoracic aortic aneurysm as the trauma is much less than in open surgery. In our own personal series no specific workup for coronary heart disease has been made and the mortality of stentgrafting of the thoracic aorta was 2.4%. A survey of the world literature, including elective and acute dissections and aneurysms revealed 642 patients treated with stentgraft with a mortality of 6.2%, although no cardiologic work up had been performed. These numbers compete well with those of open surgery, but a systematic prospective comparison would be needed in order to state the real mortality in both groups.

Transvalvular in vivo gradients of the new generation bileaflet heart valve prosthesis St. Jude Medical Regent in aortic position.

BACKGROUND: By changing the design of the St. Jude Medical Regent prosthesis in shifting both sewing cuff and retaining ring into a completely supra-annular position, the Regent valve has a greater geometric orifice for a given outer diameter. Accordingly, in vitro studies have shown increased effective orifice areas (EOAs) and lower transvalvular gradients. The aim of our study was to determine in vivo transvalvular gradients and EOAs in patients after aortic valve replacement (AVR). METHODS: We investigated 75 patients at 12 to 21 months follow-up after AVR using transthoracic echocardiography. We determined left ventricular systolic and diastolic function, EOA, and transvalvular peak gradient parameters at rest. Outcomes were assessed using the NYHA classification and functional status. RESULTS: No patient experienced cardiac failure. The majority reported good functional status and good quality of life. Five (6.7 %) late deaths were observed within the surveillance period. At follow-up, 92 % of the patients had improved by at least one NYHA class. Transvalvular peak gradients at rest for patients with Regent valves were 25.4 +/- 7.7 mmHg, 19.2 +/- 4.6 mmHg, 15.6 +/- 5.8 mmHg, 14.6 +/- 5.5 mmHg, and 8.5 +/- 2.5 mmHg; EOAs were 1.38 +/- 0.32 cm2, 1.62 +/- 0.49 cm2, 2.24 +/- 0.83 cm2, 2.63 +/- 0.70 cm2, and 3.28 +/- 0.34 cm2 for valve sizes 19 mm, 21 mm, 23 mm, 25 mm, and 27 mm, respectively. CONCLUSIONS: The SJM Regent valve shows excellent in vivo hemodynamics as confirmed by echocardiography. Clinically, 92 % of the patients improved by at least one NYHA class.

Cardiopulmonary bypass copolymer surface modification reduces neither blood loss nor transfusions in coronary artery surgery.

OBJECTIVE: Surface-modifying additives (SMA) have been suggested for improving cardiopulmonary bypass (CPB) circuit biocompatibility, potentially minimizing inflammatory complications and bleeding associated with CPB. The purpose of this prospective, randomized clinical study was to compare a novel copolymer surface-modified CPB circuit (SMARXT; COBE Cardiovascular) against the unmodified circuit. METHODS: We randomized 122 patients with isolated coronary artery disease subjected to first-time surgery on CPB into either the SMA (n = 62) or the control group (n = 60). Exclusion criteria included renal insufficiency, liver disease, coagulopathy, anticoagulation therapy < 6 days preop, carotid artery stenosis > 70 %, and a history of stroke. We collected perioperative clinical data including drainage blood loss, transfusion requirements, duration of mechanical ventilation, and ICU stay. Platelet function was determined pre- and post-CPB. RESULTS: SMA patients received 3.2 +/- 0.9 (SD) grafts during 48 +/- 16 min of aortic cross clamp and 91 +/- 30 min CPB (Control: 3.0 +/- 0.9 grafts; p = 0.33, 46 +/- 14 min AXC; p = 0.36, and 84 +/- 23 min CPB; p = 0.14). In the SMA group, 23 patients (37 %) received red blood-cell transfusions, 9 patients (15 %) fresh frozen plasma, and 3 patients (5 %) received platelets (control: n = 27 [46 %], p = 0.44; n = 10 [17 %], p = 0.91; and n=4 [7 %], p = 0.71, respectively). Platelet count on CPB fell to the same level in both groups. In SMA patients, platelet function decreased from 94.2 +/- 24.9 % pre-CPB to 79.5 +/- 32.8 % post-CPB (p = 0.043) (control: from 87.7 +/- 25.6 % to 69.4 +/- 34.7 %; p = 0.001). Postoperative drainage blood loss, mechanical ventilation duration, and ICU stay were similar in both groups (p > 0.3). One patient of the control group was excluded due to surgical bleeding, and one SMA patient died. CONCLUSIONS: Our results show that the surface-modified CPB circuit decreased neither blood loss nor transfusions despite slightly better platelet function preservation compared to the unmodified circuit. This type of CPB circuit surface modification does not appear to improve clinical outcome in low-risk coronary artery surgery patients.

Impact of myocardial protection during coronary bypass surgery on patient outcome.

We have recently shown that continuous coronary perfusion with warm blood enriched with the ultra-short acting beta-blocker Esmolol (ES) improves functional and structural myocardial protection during coronary artery surgery as compared with conventional cardioplegia (CP). The purpose of the present study was to compare both myocardial protection techniques in terms of patient outcome. We retrospectively analyzed the charts of 150 consecutive patients subjected to coronary artery surgery using the ES-technique; 150 patients matched for age, gender, preoperative left ventricular function, history of renal failure, and history of neurological symptoms undergoing surgery with conventional CP during the same time period served as control group. There were no significant differences between both groups with respect to perioperative myocardial infarction rate, need for positive inotropic medication, need for mechanical circulatory support, duration of mechanical ventilation, duration of intensive care unit stay, time of mobilization, postoperative renal failure, cardiac arrhythmias, neurological symptoms, infections or in-hospital mortality. ES-patients were less frequently readmitted to the intensive care unit (ES: 3/150; 2.2% [95% confidence interval: 0-4.2%] vs. CP: 13/150; 8.7% [4.2-13.2%]; P=0.010) and total hospital stay was shorter (ES: 12.3+/-4.8 days [95% CI: 11.5-13.0] vs CP: 13.5+/-3.8 [12.9-14.1] days; P=0.0013), thus saving 159 patient days on the normal ward. Procedural costs were less for the ES-technique (US$ 60 per patient) as compared to the cardioplegia technique (US$ 120 per patient). These data suggest that myocardial protection using the ES-technique does not improve clinical outcome in patients subjected to routine coronary artery surgery, but may save costs.

Characterization of beta(1)-selectivity, adrenoceptor-G(s)-protein interaction and inverse agonism of nebivolol in human myocardium.

Intrinsic activity and beta(1)-selectivity are important features of beta-blockers in the treatment of patients with coronary syndromes and heart failure. In human myocardium, intrinsic activity and beta(1)-selectivity of the novel beta-adrenoceptor antagonist nebivolol have not yet been determined. The study examines intrinsic activity, beta-adrenoceptor-G-protein coupling and beta(1)-selectivity of nebivolol and bisoprolol in human ventricular myocardium. Furthermore, intrinsic activity of both compounds is compared to the one of bucindolol, carvedilol and metoprolol in human atrial myocardium. Radioligand binding studies ([(125)I]-lodocyanopindolol) were performed on membrane preparations of human failing and nonfailing myocardium and on COS-7 cells transfected with human beta(1)- and beta(2)-adrenoceptors, respectively. Functional experiments were carried out on isolated muscle preparations of human left ventricular and right atrial myocardium from failing and nonfailing hearts. Radioligand binding studies reveal 3 - 4 fold beta(1)-selectivity for nebivolol and 16 - 20 fold beta(1)-selectivity for bisoprolol in human myocardium. In COS-7-cells, beta(1)-selectivity is 3 fold for nebivolol and 15 fold for bisoprolol. Neither the binding of nebivolol nor of bisoprolol is affected by the presence of guanylylimidodiphosphate (Gpp(NH)p). Nebivolol and bisoprolol exert similar inverse agonist activity in human ventricular as well as atrial myocardium. In atrial myocardium, inverse agonism of both compounds is higher compared to bucindolol, equal to carvedilol and lower compared to metoprolol. Favourable haemodynamic effects of nebivolol in humans are not due to beta(1)-selectivity or partial agonist activity of this agent. Other mechanisms, i.e. the production of nitric oxide, may thus be responsible for its unique haemodynamic profile.

The ultrarapid and the transient outward K(+) current in human atrial fibrillation. Their possible role in postoperative atrial fibrillation.

Atrial fibrillation (AF) causes distinct changes in atrial conduction, characterized as electrical remodeling. Experimental data on the possible significance of alterations of specific K(+)outward currents in this process are still limited in human AF. The ultra-rapid delayed rectifier current (I(Kur)) has not been studied in AF with respect to its sensitivity to 4-Aminopyridine (4-AP). To clarify the role of (1) the 4-AP sensitive I(Kur)current, compared to recordings without using 4-AP (I(Kur*)), and (2) the transient outward current (I(to)) in changes of atrial repolarization associated with AF, whole cell voltage-clamp recordings were obtained from atrial myocytes of patients undergoing elective cardiac surgery, with and without a history of atrial fibrillation (AF/non-AF). Further, a possible relation between experimental data and postoperative AF was studied. In AF patients, I(Kur*)was reduced by 40% [5.00+/-0.32 pA/pF (non-AF) and 2.91+/-0. 45 pA/pF (AF) at +50 mV, P<0.0001, n=22/11], I(Kur)by 55% [3.81+/-0. 30 pA/pF (non-AF) and 1.71+/-0.20 pA/pF (AF) at +50 mV, P<0.0001, n=22/11]. The mean amplitude of I(Kur)was significantly smaller than I(Kur*). Consistently, I(to)was reduced by 44% [11.57+/-0.77 pA/pF (non-AF) and 6.51+/-1.31 pA/pF (AF), P<0.01, n=25/11]. In 48% of non-AF patients, postoperative AF was detected. The corresponding voltage-clamp recordings showed a trend to reduced I(Kur*)and I(Kur)currents, although it did not reach statistical significance. The consistent reduction of all three K(+)currents investigated due to the presence of AF indicates an important association of abnormalities in cellular repolarization with the onset and the self-sustaining nature of human AF.

[Risk stratification in heart surgery: do risk scores facilitate the determination of indications?]. / Risikostratifizierung in der Herzchirurgie--Entscheidungshilfe bei der Indikationsstellung.

Various risk scores have been developed for the assessment of operative risk in cardiac surgery. Although risk stratification has been acknowledged as a useful tool to analyze trends in therapy and changes in patient populations, its relevance in assessing the indication for surgery has been questioned. It was the goal of this prospective study to compare 6 common risk scores with regard to the predictive value for mortality in individual patients. Between September 1998 and February 1999 all adult patients undergoing heart surgery were prospectively scored according to the following scores: initial Parsonnet, Cleveland Clinic, French, Euro, Pons, and the Ontario Province Risk score. Early lethality was assessed within 30 days postoperatively. Follow-up was completed in 504 patients. With the exception of the Ontario Province Risk score, lethality in the high risk group was overestimated by all scores, whereas lethality in low to moderate risk groups was underestimated by several scores. Mean scores of surviving and deceased patients showed a broad overlap with high standard deviations. Preoperative risk scores are effective tools for stratification of patient populations and the analysis of surgical outcome. With the aid of risk scores, operative risk can be sufficiently predicted for patient populations or subpopulations. The Euro score best predicted the outcome of our patients. However, when the indication for surgery is to be determined in an individual patient, risk scores should be only considered as an orientation in the decision process.

Different intrinsic activities of bucindolol, carvedilol and metoprolol in human failing myocardium.

1. Clinical studies have shown different effects of beta-blockers on the beta-adrenergic system, tolerability and outcome in patients with heart failure. 2. The study examines beta-adrenoceptor-G-protein coupling and intrinsic activity of bucindolol, carvedilol and metoprolol in human ventricular myocardium. 3. Radioligand binding studies ([(125)I]-Iodocyanopindolol) were performed in membrane preparations of human failing and nonfailing myocardium. Functional experiments were carried out in isolated muscle preparations of human left ventricular myocardium from failing hearts. 4. Bucindolol and carvedilol bound non-selectively to beta(1)- and beta(2)-adrenoceptors and exerted guanine nucleotide modulatable binding. Metoprolol was 35-fold beta(1)-selective and lacked guanine nucleotide modulatable binding. 5. All beta-blockers antagonized isoprenaline-induced enhancement of contractility. 6. In preparations in which the coupling of the stimulatory G-protein to adenylate cyclase was facilitated by forskolin, bucindolol increased force of contraction in three and decreased it in five experiments. Carvedilol increased force in one and decreased it in six experiments. Metoprolol decreased force in all experiments by 89. 4+/-2.2% (P<0.01 metoprolol vs carvedilol and bucindolol). The negative inotropic effect of metoprolol was antagonized by bucindolol. 7. It is concluded that differences in intrinsic activity can be detected in human myocardium and have an impact on cardiac contractility. In human ventricular myocardium, bucindolol displays substantially higher intrinsic activity than metoprolol and carvedilol. Bucindolol can behave as partial agonist or partial inverse agonist depending on the examined tissue. 8. Differences in intrinsic activity may contribute to differences in beta-adrenoceptor regulation and possibly to differences in tolerability and outcomes of patients with heart failure.

Risk stratification in heart surgery: comparison of six score systems.

OBJECTIVE: Risk scores have become an important tool in patient assessment, as age, severity of heart disease, and comorbidity in patients undergoing heart surgery have considerably increased. Various risk scores have been developed to predict mortality after heart surgery. However, there are significant differences between scores with regard to score design and the initial patient population on which score development was based. It was the purpose of our study to compare six commonly used risk scores with regard to their validity in our patient population. METHODS: Between September 1, 1998 and February 28, 1999, all adult patients undergoing heart surgery with cardiopulmonary bypass in our institution were preoperatively scored using the initial Parsonnet, Cleveland Clinic, French, Euro, Pons, and Ontario Province Risk (OPR) scores. Postoperatively, we registered 30-day mortality, use of mechanical assist devices, renal failure requiring hemodialysis or hemofiltration, stroke, myocardial infarction, and duration of ventilation and intensive care stay. Score validity was assessed by calculating the area under the ROC curve. Odds ratios were calculated to investigate the predictive relevance of risk factors. RESULTS: Follow-up was able to be completed in 504 prospectively scored patients. Receiver operating characteristics (ROC) curve analysis for mortality showed the best predictive value for the Euro score. Predictive values for morbidity were considerably lower than predictive values for mortality in all of the investigated score systems. For most risk factors, odds ratios for mortality were substantially different from ratios for morbidity. CONCLUSIONS: Among the investigated scores, the Euro score yielded the highest predictive value in our patient population. For most risk factors, predictive values for morbidity were substantially different from predictive values for mortality. Therefore, development of specific morbidity risk scores may improve prediction of outcome and hospital cost. Due to the heterogeneity of morbidity events, future score systems may have to generate separate predictions for mortality and major morbidity events.

Absence of hemodynamic and ECG changes in a patient with traumatic left ventricular injury and puncture of the left anterior descending branch.

Patients with penetrating cardiac injury usually present with cardiac tamponade and shock upon hospital arrival. However, absence of hemodynamic depression does not exclude a potentially fatal injury of the heart. This article reports on a patient who developed neither hemodynamic depression nor ECG changes for several hours, despite two left ventricular lacerations with puncture of the LAD. Echocardiography is advocated as the diagnostic tool of choice, and it is emphasized that no penetrating objects should be removed from the wound before surgical access to the heart is established, as this may result in the sudden development of cardiac tamponade.

Simultaneous carotid and coronary artery surgery: indications and perioperative outcome.

BACKGROUND: A significant number of patients with coronary artery disease is diagnosed with additional carotid artery disease. This subset of patients has been identified as a high-risk group for cardiac and cerebral complications following surgical intervention. METHODS: In a retrospective analysis we investigated the perioperative outcome of combined single-stage carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in 63 patients operated between January 1989 and August 1998. In all of these patients, CEA was performed prior to CABG and before initiation of cardiopulmonary bypass. RESULTS: Perioperative mortality rate was 7.9% (5/63) for simultaneous CEA and CABG and was due to cardiac complications in all patients. Postoperative unilateral neurological symptoms were diagnosed in 1 patient (1.7%) and were completely reversible. No neurologic events suggestive for permanent cerebral damage were observed during the 30 d postoperative period. CONCLUSIONS: In our study combined single-stage CEA and CABG was associated with low cerebral morbidity and patient outcome was mainly determined by cardiac complications. In this subset of patients, simultaneous CEA and CABG appears to be a safe method.

Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery.

The authors' recent experimental work has demonstrated that myocardial protection using continuous coronary perfusion with warm beta-blocker-enriched blood avoids myocardial ischaemia and minimizes myocardial oedema formation, thus completely preserving left ventricle function. The purpose of this clinical study was to compare this alternative technique in terms of structural and functional myocardial protection with the routinely used crystalloid Bretschneider cardioplegia. Sixty coronary artery surgery patients were randomized to receive either crystalloid cardioplegia or continuous coronary perfusion with warm blood enriched with the ultra-short acting beta-blocker esmolol. Cardiac function was evaluated using transoesophageal echocardiography (fractional area of contraction) and cardiac metabolism using arterial-coronary sinus lactate concentration difference (a - csD(LAC)). From left ventricular biopsies, the authors determined myocardial oedema, heat-shock-protein-70, intercellular-adhesion-molecule and actin pattern. Patients with crystalloid cardioplegia received 3.6 +/- 0.8 grafts during 64 +/- 20 min cross-clamp time (beta-blocker: 3.5 +/- 0.9 grafts during 68 +/- 22 min; NS). Following cross-clamp removal crystalloid cardioplegia hearts released significant lactate amounts (a- csD(LAC)) - 1.0 +/- 0.6 versus - 0.1 +/- 0.2 mmol/litre in beta-blocker hearts; P < 0.05). In crystalloid cardioplegia hearts, myocardial water content increased from 82.1 +/- 2.1% pre-cardiopulmonary bypass to 83.2 +/- 1.7% at the end of cardiopulmonary bypass (P < 0.05); in beta-blocker hearts myocardial water content remained unchanged (pre-cardiopulmonary bypass: 82.3 +/- 1.9%; end of cardiopulmonary bypass: 82.4 +/- 1.7%; NS). At the end of cardiopulmonary bypass, left ventricular biopsies of beta-blocker hearts showed less structural damage as determined by heat shock protein-70, intercellular adhesion molecule-I and deranged actin cross-striation pattern as compared with crystalloid cardioplegia hearts (P < 0.05). The post-cardiopulmonary bypass fractional area of contraction was similar in both groups (beta-blocker: 65 +/- 14%; crystalloid cardioplegia: 62 +/- 16%); however, beta-blocker patients required less inotropic stimulation (dopamine: beta-blocker: 2.9 +/- 2.5 versus crystalloid cardioplegia: 5.0 +/- 2.3 microg/kg per min; P < 0.05). The data suggest that continuous coronary perfusion with warm esmolol-enriched blood results in better myocardial protection compared with crystalloid cardioplegia. It is concluded that the concept of beta-blocker-induced cardiac surgical conditions may be a useful alternative for myocardial protection during coronary artery surgery.

Effect of beta-blockers on free radical-induced cardiac contractile dysfunction.

BACKGROUND: We examined the effects of hydroxyl radicals (OH.) on human myocardial contractility and on sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) activity and the effects of the beta-receptor antagonists metoprolol, carvedilol, and its metabolite BM-910228. METHODS AND RESULTS: Isometric force of contraction was determined in isolated human myocardium. H(2)O(2) 1 mmol/L and Fe(3+)-nitrilotriacetic acid (Fe(3+)-NTA) 0.1 mmol/L used for generation of OH. induced a decrease in basal force of contraction and an increase in diastolic tension in atrial and left ventricular myocardial preparations. After challenge with OH., the maximum positive inotropic response to Ca(2+) 1.8 to 15 mmol/L was decreased by 60% and by 39%, respectively. The effects of OH. could be blocked by catalase. Carvedilol and its metabolite BM-910228 attenuated the OH.-induced impairment of the inotropic response to Ca(2+) in atrial myocardial preparations. Metoprolol had no significant effect. The stimulation frequency (0.5 to 3.0 Hz)-dependent increase in force of contraction and decrease in diastolic tension were abolished after exposure of atrial trabeculae to OH. In parallel, SERCA activity was decreased by OH. concentration-dependently, as determined in myocardial membrane preparations. BM-910228 partially restored the force-frequency relationship and preserved SERCA activity. CONCLUSIONS: OH. radicals induce an impairment of contraction and relaxation and an attenuation of the force-frequency relationship in human myocardium accompanied by an inhibition of SERCA. Carvedilol and BM-910228 partly prevented OH.-induced contractile dysfunction. These observations could explain the improvement of ejection fraction in heart failure trials with carvedilol without a restoration of beta-adrenergic receptor density.

Intracoronary shunt insertion prevents myocardial stunning in a juvenile porcine MIDCAB model absent of coronary artery disease.

OBJECTIVE: The relevance of regional LV myocardial ischemia/reperfusion induced by temporary left anterior descending (LAD) coronary artery occlusion during minimally invasive direct coronary artery bypass (MIDCAB) grafting is controversial. The purpose of our study was (1) to determine the impact of conventional LAD occlusion during left internal thoracic artery (LITA)-LAD anastomosis on regional LV myocardial ischemia and function, and (2) to evaluate if intra-LAD shunt insertion during LITA-LAD anastomosis prevents potential regional LV ischemia and dysfunction in a pig model. METHODS: In 20 anesthetized, mechanically ventilated pigs we performed LITA-LAD anastomosis on the beating heart without cardiopulmonary bypass during either 15 min LAD occlusion (occlusion-group; n = 10) or 15 min intra-LAD shunt insertion to maintain blood supply to the myocardium beyond the anastomosis (shunt-group; n = 10). Besides standard hemodynamics we determined the global and regional LV wall motion score index (WMSI) using epimyocardial echocardiography. To quantitate structural myocardial alteration we determined the inducible heat-shock protein-70 (HSP-70) in LV anterior wall myocardial biopsies. Data were recorded at baseline, at 15 min of LAD occlusion or shunt insertion, respectively, and at 30 min of reperfusion. At the end of the experiments we determined myocardial adenine nucleotide (ATP, ADP, AMP) and glycogen content. RESULTS: In both groups WMSI was not significantly different at 15 min LAD occlusion or shunt insertion, respectively, as compared to baseline. However, at 30 min reperfusion both global and regional WMSI demonstrated significant LV dysfunction in the occlusion-group, whereas LV function in the shunt-group remained normal. This was associated with higher myocardial HSP-70 expression in the occlusion-group (P < 0.05). Myocardial adenine nucleotide and glycogen contents were significantly better preserved in the shunt-group. CONCLUSIONS: Our data show that in a porcine MIDCAB model 15 min LAD occlusion and 30 min reperfusion result in significant myocardial stunning. In contrast, maintenance of LAD perfusion using intracoronary shunt insertion minimizes ischemia/reperfusion injury and prevents regional LV dysfunction. Although our experiments were conducted in healthy pig hearts absent from coronary artery disease, similar results may--at least partially--be expected in humans, and thus, intracoronary shunts could be a useful tool for myocardial protection during 'off-pump revascularization'.

Effects of endotoxin on human myocardial contractility involvement of nitric oxide and peroxynitrite.

OBJECTIVES: This study examined the effects of endotoxin on cardiac contractility in human myocardium. BACKGROUND: In animal myocardium, endotoxin and cytokine treatment led to enhanced inducible nitric oxide synthase (iNOS) expression and contractile dysfunction. Effects in human myocardium are unknown. METHODS: Left ventricular myocardial preparations from failing (n = 18) and nonfailing (n = 5) human hearts were incubated for 6 and 12 h in tyrode solution or in tyrode plus lipopolysaccharides (LPS), with LPS plus N(G)-mono-methyl-L-arginine (L-NMMA), with LPS plus hemoglobin or with LPS plus the superoxide scavenger 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron). Force of contraction in response to isoprenaline (0.001 to 3 micromol/liter) was determined in electrically stimulated muscle preparations. The iNOS mRNA expression was examined by in situ hybridization and by polymerase chain reaction. The cyclic guanosine monophosphate (cGMP) levels were determined by radioimmunoassay. RESULTS: Isoprenaline concentration dependently increased force of contraction. Six and 12 hours of LPS treatment of failing myocardium decreased maximum inotropic response to isoprenaline by 54% (p = 0.009) and by 69% (p = 0.0023), respectively. In nonfailing myocardium, 12 h of LPS treatment decreased maximum inotropic effect of isoprenaline by 66% (p < 0.001). The LPS effects were attenuated by L-NMMA, hemoglobin and also Tiron. The iNOS mRNA was expressed in all LPS-treated preparations but also in most control myocardial preparations. In situ hybridization revealed iNOS expression within cardiac myocytes. There was no increase in myocardial cGMP content in response to endotoxin. CONCLUSIONS: Endotoxin exposure of human myocardium leads to a depression of cardiac contractility, which is mediated by enhanced iNOS activity and release of nitric oxide (NO). Consecutive reaction of NO with superoxide and formation of peroxynitrite may contribute to the decrease in force of contraction.