Cessation of pulmonary and coronary secretion of adrenomedullin peptides in the progression of human heart failure.

In human heart failure (CHF), adrenomedullin (AM) counteracts vasoconstriction and sodium retention. We investigated circulating levels of proadrenomedullin N-20 peptide (PAMP) and AM, and left ventricular expression of preproAM and calcitonin receptor-like receptor (CRLR) mRNA. Peptide levels were determined from the left ventricle, pulmonary artery, coronary sinus, and antecubital vein in patients demonstrating severe CHF (n = 12; mean +/- SEM cardiac index, 1.9 +/- 0.2 l/min/m(2); pulmonary wedge pressure, 32 +/- 1 mmHg), moderate CHF (n = 11; cardiac index, 2.9 +/- 0.2; pulmonary wedge pressure, 14 +/- 2), and in controls (n = 11). Left ventricular mRNA was quantified using RT-PCR and Southern blot hybridization. Depending on sites of measurement, PAMP and AM in severe CHF were 1.3 - 2.0 and 1.2 - 1.9 times as high as in moderate CHF, and 3.8 - 4.6 and 2.3 - 2.8 times as high as in controls. Only patients with moderate CHF demonstrated pulmonary and coronary net release of both peptides, that is, significant step-ups in concentrations between the pulmonary artery, left ventricle, and coronary sinus. In failing ventricles, preproAM mRNA increased 2.9 times above control, but CRLR mRNA was unchanged. Altogether, the heart and the lungs release AM peptides in moderate CHF. This secretion breaks down in severe CHF: a process that may contribute to and indicate decompensation. Unlike AM, the CRLR is not transcriptionally upregulated in severe CHF.

Prevention of venous graft sclerosis with clopidogrel and aspirin combined with a mesh tubing in a dog model of arteriovenous bypass grafting.

OBJECTIVE: to investigate the effect of clopidogrel combined with aspirin or aspirin alone on fibromyointimal hyperplasia (FIMH) in a bypass model with native vein grafts (NVG) and biocompound grafts (BCG). DESIGN: twelve Beagle dogs were randomised into two equal groups. In each animal NVG and a BCG were interposed in the common carotid arteries. Postoperatively, Group 1 received clopidogrel (200 mg/d) and aspirin (100 mg/d) and Group 2 received aspirin (100 mg/d) alone. METHODS: the BCG was constructed by sheathing the ipsilateral jugular vein with highly flexible metal mesh tubing. After 30 days the grafts were harvested and pressure fixed. FIMH was determined by morphometry. RESULTS: the average wall thickness of the BCG was significantly lower than that of the NVG in both groups (0.26 (SD)0.02 mm vs 0.47 (SD)0.15 mm, p = 0.04 and 0.28 (SD)0.05 mm vs 0.70 (SD)0.29 mm, p = 0.01, respectively). For BCG treated with aspirin, the wall cross section area was lower (5.0 (SD)0.6 mm(2)vs 9.1 (SD)3.3 mm(2), p = 0.02) and the lumen larger (25.2 (SD)5.9 mm(2)vs 9.7 (SD)3.4 mm(2), p < 0.01) than for the NVG. There was also a difference in the lumen cross section area of the NVG, which was larger after combined therapy with clopidogrel and aspirin (17.9 (SD)7.8 mm(2)vs 9.7 (SD)3.4 mm(2), p = 0.04). CONCLUSIONS: in this dog model the sheathing of vein grafts effectively prevents FIMH following bypass surgery. Clopidogrel is effective in NVG.

Activation of the cardiac renin-angiotensin system and increased myocardial collagen expression in human aortic valve disease.

OBJECTIVES: We sought to determine whether the cardiac renin-angiotensin system (RAS) is activated in human aortic valve disease depending on left ventricular function, and we analyzed the concomitant regulation of the extracellular matrix components. BACKGROUND: In animal models with pressure or volume load, activation of the cardiac RAS increases fibrosis. In human aortic valve disease, the ventricular collagen protein content is increased, but only scarce data on the activation state of the cardiac RAS and its effects on collagen and fibronectin messenger ribonucleic acid (mRNA) are available. METHODS: In left ventricular biopsies from patients with aortic valve stenosis (AS) and aortic valve regurgitation and from control subjects, we quantitated mRNAs for angiotensin-converting enzyme (ACE), chymase, transforming growth factor-beta1 (TGF-beta1), collagen I, collagen III and fibronectin by reverse-transcription polymerase chain reaction. Proteins were localized by immunohistochemistry; ACE activity was determined by high performance liquid chromatography; and TGF-beta protein by quantitative enzyme immunoassay. RESULTS: Protein, ACE and TGF-beta1 mRNA were significantly increased in patients with AS and AR (1.5- to 2.1-fold) and correlated with each other. The increase occurred also in patients with normal systolic function. Collagen I and III and fibronectin mRNAs were both upregulated about twofold in patients with AS and AR. In AS, collagen and fibronectin mRNA expression levels were positively correlated with left ventricular end-diastolic pressure and inversely with left ventricular ejection fraction (LVEF). CONCLUSIONS: In human hearts, pressure and volume overload increases cardiac ACE and TGF-beta1 in the early stages. This activation of the cardiac RAS may contribute to the observed increase in collagen I and III and fibronectin mRNA expression. The increase in extracellular matrix already exists in patients with a normal LVEF, and it increases with functional impairment.

The biocompound method in coronary artery bypass operations: surgical technique and 3-year patency.

BACKGROUND: Complete arterial revascularization may be unsafe in patients with a high operative risk. In patients with varicose ectatic veins, the biocompound technique, which uses unsuitable autologous veins, enables the surgeon to influence the bypass graft wall stress levels and diameter. This report summarizes the 3-year patency of 53 patients, the survival rate of 200 patients, and operative technical considerations. METHODS: Biocompound grafts were used for aortocoronary bypass in 200 patients who were considered inappropriate subjects for complete arterial revascularization and who had unsuitable saphenous veins. RESULTS: The mortality rate (30 days) of 200 patients was 3.5%. The 3-year survival rate was 88.5%. The patency rate of the left internal thoracic artery (LITA) after 3 years was 97.3%, of the native vein was 68.7%, and of the biocompound graft was 68.3%. The LITA showed a superior patency rate (p = < 0.05). CONCLUSIONS: The LITA is the first choice in coronary bypass operation. The biocompound technique is a reliable method to achieve complete revascularization in patients with a lack of suitable saphenous veins.

Reinforcing the conventional sternal closure.

Sternal infection is a devastating complication of heart surgery. It may be the result of unstable osteosynthesis, caused by the sternal wires cutting into the cortical layers, which results in tension loss and gap formation. We describe a technique that prevents the cerclages from cutting into the sternal plates and covers the sternum with a well-capillarized barrier of major pectoralis muscle.

Angiotensin II directly increases transforming growth factor beta1 and osteopontin and indirectly affects collagen mRNA expression in the human heart.

OBJECTIVES: Angiotensin II (Ang II) induces fibroblast proliferation and collagen synthesis in the myocardium, but its precise mechanisms of action in human hearts are still unknown. Therefore, we investigated whether Ang II directly affects the collagen mRNA content in the human myocardium and in isolated human cardiac fibroblasts or whether the growth factors TGFbeta-1 and osteopontin are involved in this process. METHODS AND RESULTS I: In a first set of experiments, the direct effect of Ang II on collagen I, TGFbeta-1 and osteopontin mRNA content in fresh samples of human atrial myocardium was determined by the use of a short stimulation period. After 4 h, Ang II-stimulated atrial samples gave a significantly higher expression of both TGFbeta-1 (183+/-21% of control, p<0.05) and osteopontin mRNA (275+/-58%, p<0.02) than the controls. In contrast, the expression of collagen I mRNA was unchanged (95+/-8%). Stimulation with TGFbeta-1 led to an increase in collagen I and III mRNA (127+/-10%, p<0.05; 140+/-15%, p<0.02). METHODS AND RESULTS II: In a second protocol, to assess the effects of longer stimulation periods, we determined the effects of Ang II and its potential mediator TGFbeta-1 on collagen I, III and fibronectin mRNA expression and on proliferation of cultured human cardiac fibroblasts. Ang II caused a dose-dependent stimulation of proliferation but did not affect collagen I, II or fibronectin mRNA content after 24 h. In contrast, TGFbeta-1 stimulation significantly increased collagen I and III mRNA expression (124+/-5% and 128+/-5%, p<0.002). CONCLUSIONS: In the human heart, Ang II does not directly increase collagen or fibronectin mRNA, but it does increase TGFbeta-1 and osteopontin mRNA expression. Since TGFbeta-1 induces collagen I and III mRNA in atrial samples and in isolated cardiac fibroblasts, it may represent a necessary mediator of the Ang II effects in the human heart.

Reduction of intimal and medial thickening in sheathed vein grafts.

BACKGROUND: Arterial pressures are described as an important factor in the development of graft degeneration and in reduced patency rate in vein bypass grafts. Sheathing of the graft with a pressure resistant mesh tubing might slow down this development. METHODS: Saphenous vein grafts were implanted into the carotid arteries of five pigs in order to evaluate the influence on myointimal hyperplasia of a compliant Phynox mesh tubing (a wrought Cobalt-Chromium-Nickel-Molybdenum-Iron Alloy), which surrounded autologous vein grafts that were exposed to arterial pressure. Each pig was operated on using a sheathed vein graft (biocompound-graft, a hybrid vascular prosthesis) on one side and an untreated saphenous vein on the other. RESULTS: After 4 weeks intimal hyperplastic changes were found in all histological sections. The wall thickness (medial and intimal layer) varied from 351 microm to 432 microm in the biocompound-graft and from 391 microm to 1196 microm in the native vein grafts (p < 0.05, n = 5). Severe myocytial and fibroblast proliferation was only found in the control grafts. Cellularity of the medial layer differed at sites of maximal cellular density and ranged from 11 to 12 cells in the biocompound-graft and from 17 to 18 cells per counting field in the native vein grafts (p < 0.05, n = 5). CONCLUSIONS: External support of vein grafts reduces intimal and medial layer proliferation. The findings of this study are in accordance with the results reported by other research groups.

Expression of ACE mRNA in the human atrial myocardium is not dependent on left ventricular function, ACE inhibitor therapy, or the ACE I/D genotype.

The activity of the cardiac renin-angiotensin system is altered in human heart failure, but the regulatory mechanisms are unknown. We analyzed whether angiotensin-converting enzyme (ACE) mRNA expression in heart failure is altered in the atrial myocardium, and whether a correlation exists between atrial ACE mRNA expression and the parameters of left ventricular function. We also investigated whether the use of ACE inhibitors or the ACE I/D genotype modulates the atrial ACE mRNA content. For this purpose patients who were to undergo routine cardiac surgery were selected in a prospective manner according to left ventricular function and ACE inhibitor therapy. Samples of atrial myocardium were taken, and ACE mRNA expression was determined by internally standardized reverse transcription polymerase chain reaction. Atrial ACE mRNA expression did not differ in patients with left ventricular ejection fraction higher than 55% (2423+/-199 copies/ng RNA) and those with a value less than 45% (2661+/-143 copies/ng RNA, n.s.). ACE mRNA expression also did not differ in patients using ACE inhibitors (2585+/-175 copies/ng RNA) and those not using ACE inhibitors (2476+/-185 copies/ng RNA). Furthermore, atrial ACE mRNA expression was not affected by the ACE genotype (DD 2573+/-203, ID 2472+/-215, II 2563+/-249 copies/ng RNA). We conclude that the regulation of atrial ACE mRNA expression occurs predominantly by local mechanical or para- or autocrine factors.

[Electron-beam computed tomography in heart surgery]. / Elektronenstrahl-Computertomographie in der Herzchirurgie.

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

How to run a heart surgical unit: experiences during the first year of the Department of Cardiothoracic and Vascular Surgery, University Clinic of Regensburg.

The heart surgery unit in Regensburg was opened in June 1992. A cost analysis was done for the first year, thru May 1993 with respect to facilities, output and wages. Facilities were divided into rooms, beds and personnel. The number of rooms was constant throughout the reporting period whereas beds and personnel increased continuously. Particularly the nursing staff was expanded to meet the rising demand. A direct consequence of this progressive personnel policy was that the personnel costs also increased continuously. 644 operations were done, 542 with and 102 without a heart-lung-machine. The number of operations using a heart-lung-machine rose from 18 per month in June 1992 to 59 in May 1993. The average length of hospitalization was 13.6 days. The cost of wages per month rose from DM 166,000 initially to DM 378,000. The cost of wages per hospitalization day, however, sank from DM 740 to DM 393. Distributing non-assigned costs to the cost objects in the same relationship as assigned costs, costs per hospitalization day were as follows: Intensive care unit DM 1,233 and care unit S43 DM 193. The cost of wages per operation was estimated at DM 1,553.

The use of biocompound-grafts together with varicose veins. First clinical experience.

Complete revascularisation of patients with multivessel disease and inadequate veins is unsatisfactory despite the more frequent use of different arterial conduits. The lack of an accurate vascular prosthesis in coronary artery surgery forces to use in a certain number of patients varicose or ectatic veins. In these cases, an ultraflexible metal mesh tube is placed intraoperatively with the aid of an application set outside the harvested vein and the two joined with fibrin glue (=biocompound-graft). It reduces the graft diameter and improves the hemodynamic properties of the graft. In 18 patients with no alternative graft, 43 biocompound-bypasses were implanted. The total number of implanted bypasses is 58 (mean 3.2+/-1.0). At hospital dismission 41 of 43 biocompound-bypasses are open. One patient died 2 months after the operation. At follow-up (3.9+/-4.0 months), 16 patients are at NYHA stage I or II, one patient at stage III. The first angiographic control in one patient shows all bypasses patent. First analysis of the results encourages continuous use of the biocompound-graft. The biocompound-graft offers the surgeon the possibility of using varicose-ectatic veins if alternative bypasses are not available. Moreover, there is experimental evidence of reduced intimal hyperplasia when mechanical unloading of the vein-wall tension is performed.

[Asymptomatic endocarditis? Are consequent histological studies useful in valve surgery?]. / Asymptomatische Endokarditis? 1st eine konsequente histologische Untersuchung in der Klappenchirurgie sinnvoll?

After aortic valve replacement for endocarditis, follow-up treatment with antibiotics is imperative. However, the question of how reliable preoperative and intraoperative diagnosis of endocarditis is in cases involving aortic defects is unclear. Of the 187 patients who underwent aortic valve replacement with or without coronary bypass surgery between June 1992 and June 1994, 150 exhibited no indications of endocarditis during preoperative and intraoperative examinations. In 17 cases (Group A) histological findings indicated acute florid endocarditis in 7 patients and chronic lymphocytic endocarditis in 10. Contrarily, histological examinations of 133 patients (Group B) revealed myxoid and/or sclerotic valve degeneration. WBC and LDH activity, examined one day preoperatively and on the first and second days postoperatively, exhibited no significant differences between the two groups, with the exception of LDH activity on the first postoperative day (Group A: 490 +/- 114, Group B: 403 +/- 132, p = 0.04). Of the clinically asymptomatic patients requiring aortic valve replacement, 11.3% exhibited acute florid endocarditis upon histologic examinations. This subgroup cannot be identified based upon routine preoperative or postoperative laboratory tests or intraoperative observation. Histological examination of the aortic valve is useful for identifying the high percentage of otherwise nonidentifiable endocarditis. Further study will be required to determine therapeutic recommendations based upon such diagnosis.

[Improvement of venous diameter in bypass surgery: initial applications of ultraflexible biocompound grafts in patients]. / Optimierung des Venenquerschnitts in der Bypass-chirurgie: Erste Anwendungen des ultraflexiblen Biocompound-Grafts bei Patienten.

The use of varicose-ectatically altered veins in bypass surgery is unsatisfactory due to unfavorable flow dynamics and high closure rates. To date surgical repair possibilities to improve the flow profile of autologous vein bypasses have been limited. Using the patient's own veins to produce a biocompound graft, i.e. an ultraflexible hybrid prosthesis, is a simple method by which the surgeon can influence the profile and wall pressure of the bypass. The authors hope thus to improve the patency rate. When forming a biocompound graft, a vein is intraoperatively sheathed inside a fine ultraflexible metal mesh and the two joined with fibrin glue. The mesh hose is pulled over the entire length of the vein with the aid of an application set. Biocompound grafts were used as aorto-coronary bypasses in 9 patients (5 women, 4 men) in whom the possibility of using alternative bypasses did not exist. In 2 patients with femoro-popliteal bypass procedure the autologous varicose-ectatically altered vein was used as a biocompound-graft. Aorto-coronary bypasses: at the time of discharge from the hospital all biocompound bypasses were patent. No perioperative myocardial infarctions were observed. No wound infections occurred. Femoro-popliteal bypasses: at time of discharge from the hospital all biocompound bypasses were patent. The results prove the simplicity and reliability of this method in difficult surgical cases. The biocompound graft offers the surgeon the possibility of using varicose-ectatic veins if alternative bypasses are not available.

[Risk factors for neurologic complications in aortocoronary bypass surgery]. / Risikofaktoren für neurologische Komplikationen bei der Chirurgie des aortokoronaren Bypass.

In a prospective study risk factors for neurological complications were evaluated in 300 unselected patients undergoing open heart surgery due to coronary artery disease. Patients with combined procedure (aorto-coronary bypass graft and valve replacement) were excluded from the study. Six patients (2%) suffered from a neurological event in the early postoperative period. A strong risk factor is the age (65 +/- 6 years in the symptomatic group, 56 +/- 9 years in the asymptomatic group, p = 0.009, Student-t-test, double-sided). A certain tendency is seen in patients with carotid stenosis (17% in the symptomatic group, 5% in the asymptomatic group), in patients with a positive neurological history (17% in the symptomatic group, 1% in the asymptomatic group) and in patients with operative revision (33% in the symptomatic group, 4% in the asymptomatic group). No difference was seen in the risk factors sex, lesions of the middle cerebral artery and the ECC-time.

[Duplex and transcranial sonography in the preoperative evaluation of cerebrovascular circulation before heart operations]. / Duplex- und transkranielle Sonographie zur präoperativen Evaluation der Hirndurchblutung vor Herzoperationen.

Fifty unselected patients undergoing open heart surgery (OHS) were examined by duplex and transcranial Doppler sonography. Two high degree (greater than 75%) carotid stenosis were found in 70 carotid arteries of 35 patients with coronary artery disease. Fourteen vessels had unmistakable signs of extracranial vascular disease whilst 54 carotid arteries were identified as normal. Two high degree (greater than 75%) carotid stenosis were found in 30 vessels of 15 patients with valvular disease. Seven other vessels had a low grade stenosis or excessive atheroma, whereas 21 were identified as normal. The rate of about 5-10% asymptomatic high grade carotid stenosis in patients undergoing OHS justifies routine noninvasive examination of the cerebral circulation by duplex and transcranial Doppler sonography. Patients with high grade stenosis are offered a follow-up preventive programme against cerebral infarction, which consists of 3 steps: 1. anti-platelet aggregating drugs, 2. periodic control examinations by duplex and transcranial Doppler sonography, and 3. continued evaluation of indication for carotid endarterectomy.

[Duplex and transcranial sonography in cerebrovascular diseases]. / Duplex- und transkranielle Sonographie bei zerebrovaskulären Erkrankungen.

Duplex and transcranial sonography make non-invasive assessment of cerebrovascular hemodynamics possible. Lesions of the carotid bifurcation are divided into the categories I-VI by which the different forms of carotid lesions are defined. Pathological alterations of the major basal cerebral arteries as well as the quality of collateral circulation via the ophthalmic artery and the circle of Willis are readily picked up and evaluated by transcranial doppler sonography. If cerebrovascular disease is suspected it is therefore recommended to proceed first with duplex and transcranial sonography. If the results are negative, then echocardiography is indicated. With these non-invasive methods a correct diagnosis can usually be made. Patients who are at great risk of suffering a stroke are integrated into a programme aimed at prevention of cerebrovascular insults and re-insults. This programme includes the elimination of the usual risk factors and specifically the medication of anti-platelet drugs or oral anticoagulants respectively in cases of cardiac embolism. In special well-defined cases endarterectomy of the carotid bifurcation might be indicated. Regular clinical examinations will enable a long-term follow-up and permit assessment of the efficacy of a preventive programme while simultaneously increasing patient compliance.

Duplex scanner study of carotid artery dissection following surgical treatment of aortic dissection type A.

In patients suffering from aortic dissection, persistent perfusion of the false lumen distal to the implanted graft is frequent. Postoperative follow-up examinations of the carotid arteries of these patients were performed by duplex scanner and correlated with clinical symptoms. Thirty-nine patients who survived the surgical treatment of acute type A aortic dissection had duplex sonography of both common carotid arteries after an average postoperative follow-up of 53 months. In 21 cases a composite graft and in 18 cases a supracoronary prosthetic vascular graft were implanted. No sign of residual dissection of the common carotid arteries was seen in 23 patients; in nine there was a dissection of both common carotid arteries, and seven patients had a unilateral carotid dissection (five right, two left). There were nine symptomatic patients with the following symptoms: transient ischemic attack (four), amaurosis fugax (four), stroke with incomplete recovery (one). Two symptomatic patients had a corresponding dissection. The generally good prognosis of all these patients suggests a conservative nonoperative treatment.