[Thin-walled apical ventricular aneurysm associated with hypertrophic obstructive cardiomyopathy]. / Dünnwandiges Herzspitzenaneurysma bei hypertropher obstruktiver Kardiomyopathie.

HISTORY AND ADMISSION FINDINGS: A 73-year-old patient presented for routine follow-up examination for pre-diagnosed hypertrophic obstructive cardiomyopathy (HOCM). The patient's history included arterial hypertension and dyspnea on exertion. INTERVENTIONS: Echocardiography revealed a large apical aneurysm, which had vastly increased in size over the past six months. Further evaluation by cardiac magnetic resonance (NMR) imaging confirmed the aneurysm and demonstrated a wall thickness of no more than 2 mm. TREATMENT AND COURSE: Due to the rapid increase in size in addition to the extremely thin wall diameter the risk of spontaneous rupture was considered high and the patient was referred to surgical therapy. Echocardiographic and NMR-findings were confirmed intraoperatively. The aneurysm was resected and the postoperative progress was uneventful. CONCLUSION: Aneurysms of the apical left ventricle can result from an underlying HOCM. In case of rapid increase of the aneurysm, aneurysmectomy should be performed.

Beta-blockade in 200 coronary bypass grafting procedures.

BACKGROUND: Continuous perfusion of the coronary arteries with high-dose beta-blocker (esmolol)-enriched blood has been shown to represent an alternative for myocardial protection during coronary bypass grafting (CABG). Here, we will report on our experience in 200 unselected consecutive cases where this technique was used. METHODS: Eighty percent of the patients (age: 63.3 +/- 0.6 years, ejection fraction: 60 +/- 1.2 %, emergency cases: 11 %) had 3-vessel disease, 34 % had a history of myocardial infarction within less than 90 days preoperatively. The Euro score amounted to 6 +/- 0.3. During 52 +/- 1.2 min of aortic cross-clamp time on normothermic cardiopulmonary bypass, 2.9 +/- 0.1 distal anastomoses were performed on a slow hypocontractile beating heart induced by continuous infusion of 788 +/- 20 mg esmolol per operation. All data: mean +/- SEM. RESULTS: Postoperatively, patients were ventilated for 25 +/- 5.1 hours and stayed on ICU for 2.3 +/- 0.3 days. The postoperative myocardial infarction rate was 4%. Patients left the hospital after 11.2 +/- 0.4 days. Thirty-day mortality was 2.5 %, and 3-month mortality was 3 %. CONCLUSIONS: High-dose beta-blockade is a safe and effective technique in CABG procedures. It may be especially advantageous in high-risk patients.

Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria.

OBJECTIVES: To elucidate the structural basis for the electrophysiologic remodeling induced by chronic atrial fibrillation (AF), we investigated connexin40 and connexin43 (Cx40 and Cx43) expression and distribution in atria of patients with and without chronic AF and in an animal model of AF with additional electrophysiologic investigation of anisotropy (ratio of longitudinal and transverse velocities). BACKGROUND: Atrial fibrillation is a common arrhythmia that has a tendency to become persistent. Since gap junctions provide the syncytial properties of the atrium, changes in expression and distribution of intercellular connections may accompany the chronification of AF. METHODS: Atrial tissues isolated from 12 patients in normal sinus rhythm at the time of cardiac surgery and from 12 patients with chronic AF were processed for immunohistology and immunoblotting for the detection of the gap junction proteins. The functional study of the cardiac tissue anisotropy was performed in rat atria in which AF was induced by 24 h of rapid pacing (10 Hz). RESULTS: Immunoblotting revealed that AF did not induce any significant change in Cx43 content in human atria. In contrast, a 2.7-fold increase in expression of Cx40 was observed in AF. Immunohistologic analysis indicated that AF resulted in an increase in the immunostaining of both connexins at the lateral membrane of human atrial cells. A similar spatial redistribution of the Cx43 signal was seen in isolated rat atria with experimentally-induced AF. In addition, AF in rat atria resulted in decreased anisotropy with slightly enhanced transverse conduction velocity. CONCLUSIONS: This experimental study showed that AF is accompanied by spatial remodeling of gap junctions that might induce changes in the biophysical properties of the tissue.

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.

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.

Coronary oxygen persufflation combined with HTK cardioplegia prolongs the preservation time in heart transplantation.

BACKGROUND: One of the most restricting factors remaining in heart transplantation is the limited myocardial ischemia time. A new approach towards the prolongation of this time is the combination of primary cardioplegic arrest followed by continuous coronary oxygen persufflation (COP) with gaseous oxygen. METHODS: This technique was applied in pig hearts, which we transplanted orthotopically after cardioplegic arrest by original (n = 5) and modified (addition of hyaluronidase: n = 11) Bretschneider HTK solution and 14 h of hypothermic preservation. Depending on the different preservation techniques, we created four groups: (1), original HTK (HTK), n = 5; (2), modified HTK (mHTK), n = 5; (3), modified HTK solution plus COP (mHTK + COP), n = 6; and (4), as a control five hearts were transplanted after cardioplegic arrest by the original HTK solution and a cold ischemia time of 3 h comparable to clinical routine procedure. RESULTS: After 14 h of preservation and orthotopic transplantation, cardiac functional recovery in mHTK + COP hearts was similar to control hearts, and improved compared to hearts of both other groups. Hemodynamics were significantly better in hearts preserved by mHTK + COP and in the control group compared to the HTK-hearts (P < 0.05), not significant compared to mHTK hearts (dp/dt(max) in % of preoperative +/- standard error of mean (SEM): mHTK + COP, 85 +/- 9; control, 85 +/- 10.5; mHTK, 59 +/- 14; HTK, 50 +/- 4). The cardiac output (CO) in % of preoperative was: mHTK + COP, 68 +/- 5.4; control, 64 +/- 4; mHTK, 44 +/- 2.7; HTK, 25 +/- 11. The ATP of left ventricular myocardium in mHTK + COP hearts at 14.7 +/- 1 micromol/g dry weight (DW) and in the control at 14.59 +/- 1.8 was higher compared to that in mHTK at 12.2 +/- 2.8 (P is non-significant (n.s.) versus mHTK + COP and control) and in HTK-hearts at 7.0 +/- 0.5 (P < 0.05 versus mHTK + COP and control). CK-MB in percent of CK showed no increase in either group. CONCLUSIONS: These data show that COP combined with a mHTK solution represents a potential alternative to complement currently used cold storage techniques for prolonged preservation periods.

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.

Effects of modification of the allocation system on ischemia duration and costs of heart transplantation. Transplantation Cooperation UNI-NRW.

BACKGROUND: In order to optimize regional utilization of transplantable thoracic organs, the seven university hospitals in North-Rhine-Westfalia have formed a transplant cooperation meanwhile approved by Eurotransplant. METHODS: Heart transplant and organ donation activities of the cooperating hospitals in the year before the foundation of the cooperation (period A, 7/95 - 6/96) and in the year thereafter (period B, 7/96 - 6/97) were retrospectively analysed. RESULTS: In period A, a total of 39 heart transplants and 74 heart donations were performed, whereas in period B 67 heart transplantations and 78 heart donations could be achieved. The regional utilization of the donor organs increased from 4% to 30% with a significantly shorter ischemia time of regionally or locally allocated donor hearts than of nationally or internationally allocated ones. CONCLUSIONS: A high rate of regional or local heart transplant procedures with short ischemia times clearly demonstrate the benefits of a regionalization of heart transplant medicine for medical as well as economical reasons.

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'.

Beta-blockade versus Buckberg blood-cardioplegia in coronary bypass operation.

OBJECTIVE: Continuous perfusion of the coronary arteries with beta-blocker (esmolol)-enriched normothermic blood during cardiac surgery has been suggested as an alternative technique for myocardial protection. The aim of the present study was to compare the beta-blocker technique to Buckberg's blood cardioplegia during coronary artery bypass grafting (CABG). METHODS: Sixty patients with coronary artery disease were randomly assigned to either the esmolol group (ES, n = 30) or the blood cardioplegia group (BC, n = 30). During aortic crossclamp ES patients received continuous normothermic coronary perfusion with esmolol-enriched blood. Hearts of the BC group were protected by antegrade cold blood cardioplegia according to Buckberg. We measured left ventricular (LV) contractility using TEE (fractional area of contraction, FAC) and hemodynamic parameters prior to cannulation for cardiopulmonary bypass (CPB), after decannulation, and 4 h postoperatively. Myocardial lactate release was measured prior to aortic cross-clamp, during cross-clamp, and after decannulation. LV biopsies for determination of heat-shock protein (HSP-70), actin pattern and intercellular adhesion-molecule (ICAM-I) as indicators for structural changes were collected prior CPB, at the end of the aortic cross-clamp period, and prior to weaning off CPB. RESULTS: There was no significant difference between both groups with respect to grafts and cross-clamp time. ES hearts did not release lactate during cross-clamp. In contrast, BC hearts released significant amounts of lactate. Post CPB FAC and hemodynamics under similar inotropic stimulation showed no difference between groups, whereas at 4 h post CPB measurements showed slightly better values in the ES group: cardiac index: ES: 2.9+/-0.1 (SEM) versus BC: 2.6+/-0.1 L/min per m2 (P < 0.05); FAC: ES: 55+/-3 versus BC: 48+/-3% (P < 0.05). HSP-70 and actin pattern showed no difference between groups; however, ICAM-I showed a significantly higher degree of structural changes in BC hearts: 18+/-2 versus ES: 11+/-1% (P < 0.05). CONCLUSION: Our data demonstrate that application of the beta-blocker technique during routine CABG was associated with slightly better functional recovery and less structural myocardial alteration as compared with intermittent cold blood cardioplegia, however, both techniques provided equivalent myocardial protection in terms of patient outcome. Future studies are required to investigate if myocardial ischemia minimization by use of the beta-blocker technique may be beneficial in compromized hearts.

Excellent recovery after prolonged heart storage by preservation with coronary oxygen persufflation: orthotopic pig heart transplantations after 14-hr storage.

BACKGROUND: Improvement of heart preservation is still the greatest challenge in preservation research. The unchanged severe restriction of acceptable storage periods of heart grafts since the beginning of clinical heart transplantation indicates that technical innovations are necessary if a substantial improvement is to be achieved. METHODS: Here, we present the results of hypothermic preservation using the innovative technique of coronary oxygen persufflation (COP). COP simply adds gaseous oxygen to hypothermic graft storage and requires only a "valve guard" for reversible closure of the aortic valve. Fourteen-hr preservation was followed by orthotopic transplantation and evaluations of functional as well as metabolic recovery. Mature pig hearts, a model with restricted preservation tolerance similar to the human heart, were used to guarantee the clinical relevance of this study. RESULTS: After 14-hr hypothermic storage, COP-preserved hearts were able to recover within 2 hr of cardiopulmonary bypass to a steady cardiovascular function without mechanical or pharmacologic support. The left ventricular pressure amplitude of mHTK-COP-preserved hearts as well as energy charge potential recovered to pregrafting values and the ventricular power output to 66%. Hearts simply stored in University of Wisconsin (UW), modified Bretschneider's histidine-tryptophan-ketoglurate (mHTK), or Euro-Flush with glutathione (EFG) solution had only limited recovery, with significantly lower ventricular power output of 18%, 29% or 30% of pregrafting controls on average. CONCLUSIONS: Fourteen-hr oxygenated pig heart preservation using COP results in optimal recovery. Storage preservation in solutions containing hyaluronidase (mHTK and EFG) results in higher recoveries as compared to UW solution, an effect that may support the excellent recovery after mHTK-COP preservation.

Coronary oxygen persufflation for long-term myocardial protection.

In human heart transplantation limited myocardial ischemia duration remains one of the most restricting factors. A new approach towards prolongation of this duration is the combination of cardioplegic arrest and continuous Coronary Oxygen Persufflation (COP) with gaseous oxygen. This technique, which is based on former experiments, was applied in pig hearts which we transplanted orthotopically after a hypothermic preservation time of 14 hours. For cardioplegic arrest we used either Euro-Flush glutathion solution (EFG; n=5), University of Wisconsin solution (UW; n=5), modified Bretschneider HTK cardioplegic solution (mHTK; n=6). In preliminary experiments all three solutions had shown equal cardioprotective qualities. Hearts of the mHTK group were submitted to continuous COP during storage (mHTK+COP). After 14 hours of preservation and orthotopic transplantation the mHTK+COP hearts showed significantly improved cardiac functional recovery compared to hearts preserved by simple cold storage techniques. Hemodynamics measured after 3 hours reperfusion were significantly better in the mHTK+COP group compared to EFG and UW: dp/dtmax in % of baseline+/-standard deviation (SD): 85+/-22, 65+/-26, 36+/-15, CO in % of baseline: 68+/-13, 35+/-8, 39+/-8. Postoperative preload recruitable stroke work in the mHTK+COP hearts was: 51.4+/-23.1 mmHg compared to preoperative: 57.3+/-17.2. ATP of left-ventricular myocardium in the mHTK+COP group: 14.7+2.1 micromol/g dry weight was significantly higher compared to EFG: 10.3+/-4.5 and UW: 5.9+/-3.2. CK-MB in percent of CK in all groups showed no increase during postoperative reperfusion. This study suggests that COP may present an effective complement to cold storage techniques currently used in heart transplantation. Prior to clinical application further investigations regarding long-term survival and endothelial function are required.

Emergency coronary artery surgery after failed PTCA: myocardial protection with continuous coronary perfusion of beta-blocker-enriched blood.

BACKGROUND: Myocardial protection during cardiac surgery in patients with acute ischemia after failed PTCA remains a challenge. Our recent experimental work demonstrated that continuous coronary perfusion with warm beta-blocker-(Esmolol) enriched blood may be a useful alternative to current cardioplegia techniques, especially for compromised hearts. This technique was applied in our last 12 patients after failed PTCA (beta-B). The purpose of this retrospective study was to compare this alternative myocardial protection technique with our standard technique of cold crystalloid cardioplegia (CP). METHODS: Between January 1994 and January 1998 fifty-five patients (beta-B: n = 12; CP: n = 43) underwent emergency coronary artery bypass grafting within 24 hours after failed PTCA. The mean age in beta-B patients was 62+/-9 (SD) years, and 33% were female (CP: 59+/-9 years, 42% female, p = NS). In beta-B patients 67% had myocardial infarction (MI) prior to coronary angioplasty, 67% had an ejection fraction (EF) >55%, and coronary vessel involvement (VI) was 2.1+/-0.7. CP patients had the following findings: MI rate 42%, EF >55% in 84%, VI was 2.2+/-0.6; p = NS. Operation commenced within 25-980 min after failed PTCA. Beta-B patients received 2.7+/-0.8 grafts during 45+/-20 min continuous coronary perfusion with Esmolol enriched blood, whereas CP patients had 3.0+/-1.1 grafts in 42+/-17 min cross-clamp time, p = NS. RESULTS: The total hospital stay was significantly (p = 0.004) shorter for beta-B patients (18+/-8 days) compared to CP patients (27+/-12 days). 30-days mortality rate was 9% in CP patients, whereas none of the beta-B patients died. Postoperative low cardiac output occurred in only one patient (8%) of the beta-B group and was treated with an intra-aortic balloon pump (IABP). Eight (19%) of the CP patients required an IABP and in five (12%) patients an additional ventricular assist device was necessary (LVAD: n = 4; RVAD: n = 1). The need for circulatory support with inotropes was significantly lower in beta-B patients. Cumulative postoperative dosage of dopamine and dobutamine was 34516+/-40400 microg/kg and 16221+/-26678 microg/kg respectively in CP patients. Beta-B patients required only 12457+/-14738 microg/kg (p = 0.02) dopamine and 5112+/-7381 microg/kg (p = 0.01) dobutamine. Perioperative myocardial infarction occurred in 53% of the CP patients and 17% of beta-B patients (p = 0.046). Total CKmax was significantly (p = 0.003) higher in CP patients (812+/-531 U/L) than in beta-B patients (457+/-265 U/L). Four CP patients (9%) had acute postoperative renal failure requiring hemofiltration, and 11 CP patients (26%) had acute postoperative pneumonia. In beta-B patients one patient (8%) suffered from postoperative pneumonia (p = NS) and no patient had renal failure (p = NS). CONCLUSION: These clinical results appear to confirm our experimental data and suggest that continuous coronary perfusion with warm esmolol-enriched blood is superior to crystalloid cardioplegia in terms of in-hospital complications and mortality, especially for compromised hearts after failed PTCA.

Acute effects of nitric oxide and cyclic GMP on human myocardial contractility.

Evidence that the activity of nitric oxide synthase and the generation of nitric oxide (NO) within the myocardium are enhanced in several cardiovascular disorders is increasing. Findings whether NO exerts a direct effect on cardiac contractility are contradictory. Therefore, the direct effect of the NO donor sodium nitroprusside (SNP) on isometric force of contraction of human atrial and ventricular myocardium was investigated, and the question was addressed whether the effects of NO on cardiac contractility are mediated via cGMP. Experiments were performed on isolated electrically driven (1 Hz, 37 degrees C) human right atrial trabecula and left ventricular papillary muscle preparations from nonfailing and terminally failing hearts. SNP led to a concentration-dependent decrease of force of contraction (FOC) with a maximum effect at 100 micromol/l. In atrial trabecula, SNP (100 micromol/l) caused an acute decrease in basal FOC as well as in FOC after application of isoprenaline or IBMX by 12.5 +/- 5% (P < .05), 16.6 +/- 3.7% (P < .05) and 18.3 +/- 4.2% (P < .05), respectively. The negative inotropic effects could be attenuated by the guanylyl cyclase inhibitor methylene blue. In papillary muscle preparations, NO release caused a maximum decrease in basal and in isoprenaline-enhanced FOC of 11.0 +/- 1.9% (P < .05) and 23.6 +/- 1.5% (P < .05), respectively. In the presence of isoprenaline, the reduction of FOC was less pronounced in failing than in nonfailing papillary muscles. 8-bromo-cGMP caused a 38.2 +/- 5.2% decrease in atrial trabecula contractility. Both SNP and 8-bromo-cGMP caused a shortening of the contractile twitch with a premature onset of relaxation. As determined by radioimmunoassay, exposure of atrial trabecula to SNP (100 micromol) led to a 6-fold increase in myocardial cGMP concentrations, which could be attenuated by methylene blue. In conclusion, NO exerts a negative inotropic effect on human atrial and ventricular myocardium which seems to be mediated via generation of cGMP. The release of NO within the myocardium in a variety of cardiovascular disorders might explain decreases in cardiac contractility. The control of NO release could be an important target for future therapeutical interventions in these pathological conditions.

Evidence for functional relevance of an enhanced expression of the Na(+)-Ca2+ exchanger in failing human myocardium.

BACKGROUND: The present study aimed at investigating the expression of the Na(+)-Ca2+ exchanger and its functional role in human failing myocardium. METHODS AND RESULTS: Na(+)-Ca2+ exchanger mRNA and protein levels were examined in nonfailing (NF, n = 8) and failing human myocardium (New York Heart Association functional class IV) with idiopathic dilated cardiomyopathy (DCM, n = 8) or ischemic heart disease (ICM, n = 6). The inotropic effect of the Na+ channel activator BDF 9148 was determined in electrically driven left ventricular papillary muscle strip preparations (1 Hz, 37 degrees C) from nonfailing (n = 8) and failing (n = 8) human hearts. Na(+)-Ca2+ exchanger mRNA levels were significantly increased, by 79% (P < .001) in DCM and by 58% (P < .01) in ICM compared with NF; protein levels increased by 36% (P < .001) and by 20% (P < .05), respectively. BDF 9148 increased the force of contraction concentration dependently, with a similar maximal effect in NYHA class IV and NF, but was more potent in NYHA class IV as demonstrated by a significantly smaller (P < .01) EC50 value (NYHA class IV, 0.18 [0.16 to 0.22] mumol/L; NF, 1.65 [1.3 to 3.0] mumol/L). In NYHA class IV, BDF 9148 (0.1 mumol/L) restored the positive force-frequency relationship and reduced the frequency-dependent increase in diastolic tension in relation to force of contraction. CONCLUSIONS: The increased expression of the Na(+)-Ca2+ exchanger is a possible explanation for the increased inotropic potency of the Na+ channel activator BDF 9148 in failing human myocardium. The increase in exchanger molecules could be of functional relevance for the modulation of cardiac contractility by agents that increase the intracellular Na+ concentration. Enhancement of Na(+)-Ca2+ exchanger activity might be a powerful mechanism for increasing cardiac contractility in chronic heart failure.

Sarcoplasmic reticulum Ca2+ATPase and phospholamban mRNA and protein levels in end-stage heart failure due to ischemic or dilated cardiomyopathy.

Abnormalities in intracellular Ca2+ handling play a crucial role in the pathogenesis of heart failure. The reduced capacity of failing human myocardium to restore low resting Ca2+ levels during diastole has been explained by the impairment of Ca2+ uptake into the sarcoplasmic reticulum (SR) via the SR Ca2+ATPase. It is unclear whether Ca2+ATPase function, protein levels, and mRNA steady-state levels correspond to one other, and whether the cause of heart failure, namely idiopathic dilated or ischemic cardiomyopathy, produces different changes. The present study examined SR Ca2+ATPase activity and both mRNA and protein levels of SR Ca2+ATPase, phospholamban, and Gi alpha 2 in left ventricular myocardium from eight nonfailing hearts, from eight hearts of patients with idiopathic dilated cardiomyopathy (DCM), and from six hearts from patients with ischemic cardiomyopathy (ICM). Compared to nonfailing myocardium, the activity of the SR Ca2+ATPase was significantly reduced in failing myocardium from patients with DCM (36%, P < 0.01) and from patients with ICM (37%, P < 0.001). Significantly lower levels of SR Ca2+ATPase mRNA levels (55% and -56%, P < 0.001 for DCM and ICM, respectively) and phospholamban mRNA (45%, P < 0.001 for DCM; 31%, P < 0.05 for ICM) were observed in failing than in nonfailing myocardium. In contrast, no significant changes were observed at the level of proteins, Gi alpha 2 mRNA and protein levels were both significantly increased in failing myocardium. There were no differences between idiopathic dilated and ischemic cardiomyopathy concerning the examined parameter. It is concluded that reduced SR Ca2+ATPase activity contributes to an altered intracellular Ca2+ handling by the SR in both dilated and ischemic cardiomyopathic hearts. However, changes in SR Ca2+ATPase and phospholamban steady-state protein levels do not contribute to these alterations. The dissociation between protein and mRNA levels provides evidence for a posttranscriptional or post-translational regulation of these proteins. The observed alterations are not dependent on the underlying cause of end-stage heart failure.

Effects of angiotensin II and angiotensin-converting enzyme inhibitors on human myocardium.

Human myocardial angiotensin II receptors and the angiotensin AT1 and AT2 receptor subtypes were characterised using the partial angiotensin II receptor agonist [125I][Sar1,IIe8]angiotensin II and the selective antagonists losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2'((1H-tetrazol-5-yl)biphen yl-4-yl)- methyl]imidazole) and PD 123177 (1-[(4-amino-3-methylphenyl)methyl]-5-(diphenyl-acetyl)- 4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridine-6-carboxylic acid). The density of angiotensin II receptors was higher in atrial than in ventricular myocardium. Angiotensin AT2 receptors were predominant in atria and ventricles (80-85% of total angiotensin II receptors). Only in isolated, electrically driven atrial trabeculae but not in ventricular preparations, angiotensin II did produce a concentration-dependent positive inotropic effect, which was antagonized exclusively by the angiotensin AT1 receptor antagonist losartan and which amounted to about 20% of the positive inotropic effect of milrinone and isoprenaline. The application of the angiotensin-converting enzyme inhibitors captopril, enalaprilat and ramiprilat had no inotropic effect in either tissue. It is concluded that angiotensin AT1 receptors exclusively mediate direct positive inotropic effects in atrial myocardium. Since angiotensin-converting enzyme inhibitors do not produce any inotropic effect, tonic regulation of basal force of contraction by angiotensin II does not occur.