The search and destroy strategy prevents spread and long-term carriage of methicillin-resistant Staphylococcus aureus: results from the follow-up screening of a large ST22 (E-MRSA 15) outbreak in Denmark.

In the aftermath of a methicillin-resistant Staphylococcus aureus (MRSA) ST22 hospital outbreak, we investigated the prevalence of long-term carriage, the efficacy of MRSA decolonization treatment (DT) and the spread of MRSA to households of patients and healthcare workers (HCWs). Furthermore, we evaluated the efficacy of repeated DT in long-term MRSA carriers. Of 250 index persons (58 HCWs and 192 patients), 102 persons (19 HCWs and 83 patients) and 67 household members agreed to participate. Samples from all 169 persons were taken from the nose, throat, wounds and devices/catheters, and urine samples were additionally taken from index persons. Samples from companion animals (n = 35) were taken from the nostrils and anus. Environmental sites (n = 490) screened were telephone, television remote control, toilet flush handle, favourite chair and skirting board beside the bed. Sixteen (19%) patients and two household members, but no HCWs, were ST22-positive. The throat was the most frequent site of colonization. In a multivariate analysis, chronic disease (p <0.001) and pharyngeal carriage (p <0.001) were associated with long-term MRSA carriage. MRSA was found in the environments of four long-term carriers. All animals tested were negative. MRSA-positive households were decolonized using nasal mupirocin TID and daily chlorhexidine body and hair wash for 5 days. Pharyngeal MRSA carriers also received fucidic acid (500 mg TID) combined with rifampicin (600 mg BID) or clindamycin (600 mg BID) for 7 days. The home environment was cleaned on days 2 and 5. At the end of follow-up, ten of 16 long-term carriers and the two household contacts were MRSA-negative. In conclusion, decolonization of MRSA carriers is possible, but should include treatment of household members and the environment.

Development of Marjolin's ulcer following successful surgical treatment of chronic sacral pressure sore.

STUDY DESIGN: Case report. OBJECTIVE: Report of an unusual case, where a Marjolin's ulcer that developed 2.5 years after surgical excision and successful closure. SETTING: Department of Plastic and Reconstructive Surgery and Burn Unit and the Clinic for Spinal Cord Injuries, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. METHODS AND RESULTS: A 22-year-old man sustained a fracture with luxation of the 5th and 6th cervical vertebrae and loss of sensory and motor function after a diving accident (complete C8 lesion). During initial hospitalization, he developed a sacral ulcer, which more or less persisted for 38 years, despite several attempts of surgical and conservative treatment. At this time, the ulcer was finally excised and the wound closed successfully. Two and a half years later, however, the ulcer recurred. Biopsies showed squamous cell carcinoma and computed tomography, and magnetic resonance imaging scans revealed a soft tissue process over the sacral and coccygeal bones and massive destruction of these bony structures. The patient died 11 months later, despite surgical and radiation treatment. CONCLUSION: The present case is unusual because, in spite of surgical excision and successful closure of the wound, the patient developed Marjolin's ulcer 2.5 years later. Yet it illustrates the primary importance of preventing the development pressure sores, of aggressive (surgical) therapy with healing when they do arise and of taking frequent biopsies in longstanding chronic ulcers to procure early diagnosis and treatment.

[Sentinel node biopsy in cutaneous malignant melanoma of the lower extremities]. / "Sentinel node"-biopsi ved kutant malignt melanom på underekstremiteterne.

Although a substantial number of patients with intermediate thickness cutaneous malignant melanoma (> 1.5-4 mm) have non-detectable regional node metastases, elective regional node dissection still remains controversial. One-three specific lymph node(s)--sentinel node(s)--in the first drained regional lymphatic basin can be visualised peroperatively by applying Patent V Blue intradermally at the site of the previous melanoma. Histological examination of the sentinel node can reveal metastases and therefore presumably give a more accurate oncological staging, thus enabling selection of patients who may benefit from elective regional node dissection. The aim of the present study was to describe our experience with this technique in 23 patients treated for cutaneous malignant melanoma of the lower extremity with a thickness > 1.5 mm. We found that sentinel node dissection, through a minimal surgical procedure, was efficient in detecting micrometastases in the regional lymph node(s).

Transmitter interactions in rabbit internal anal sphincter.

The aim of the present study was to investigate the relative importance of the different putative nonadrenergic noncholinergic (NANC) mediators and their interplay with cholinergic nerves in the rabbit internal anal sphincter (IAS). IAS preparations were mounted in organ baths for recording of isometric tension. Transmural field stimulation (TMS; 5-s trains; supramaximal voltage, 140-160 V; 0.4-ms impulse duration) was applied every 2 min with frequencies varying from 0.2 to 32 Hz. TMS induced frequency-dependent relaxations that amounted to 89.3 +/- 2.2% (n = 7). N omega-nitro-L-arginine (L-NNA; 10(-7)-10(-4) M; 8 Hz) reduced relaxations and this effect was partially inhibited by preincubation with L-arginine (10(-4) M). The effect of L-NNA was attenuated by atropine preincubation. Apamin (10(-6) M) shifted the frequency-response curve to the right but left maximal relaxations in response to TMS unaffected. In the presence of L-NNA (10(-4) M) and atropine (10(-6) M), the action (area between the frequency-response curve with or without a substance) of apamin was more pronounced, but, despite the presence of both L-NNA and apamin, some relaxation still remained. The frequency-response curve (control) was significantly shifted to the right by carbachol (10(-6) M). Concentration-response experiments showed that the response to exogenous nitric oxide (NO; 10(-7)-10(-4) M) was unaffected by carbachol (10(-6) M) preincubation, whereas responses to vasoactive intestinal polypeptide (VIP) and ATP were significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological identification of different inhibitory mediators involved in the innervation of the internal anal sphincter.

1. Inhibitory non-adrenergic, non-cholinergic (NANC) responses were studied in isolated strips from the rabbit internal anal sphincter. 2. In the presence of atropine and guanethidine, transmural field stimulation induced frequency-dependent relaxations that reached a plateau at frequencies > or = 4 Hz. 3. These relaxations were inhibited by apamin (10(-6) M) and by N omega-nitro-L-arginine (L-NOARG, 10(-4) M). With these two substances in combination, relaxations were still seen in response to field stimulation, but only at frequencies > 2 Hz. 4. In the presence of both apamin (10(-6) M) and L-NOARG (10(-4) M), responses at high frequencies consisted of a fast relaxation followed by a slow return to prestimulus tension level. alpha-Chrymotrypsin hastens the return of tension to prestimulus level after high frequency stimulation. 5. Zinc-protoporphyrin IX, an inhibitor of haeme oxygenase, had a significant inhibitory effect on relaxations induced by transmural field stimulation. It was found, however, that responses to sodium nitroprusside and to isoprenaline (both 10(-9)-10(-4) M) were reduced comparably, indicating that the effect of zinc-protoporphyrin IX was unspecific. 6. It is concluded that pharmacological analysis allows identification of at least three distinguishable components of the inhibitory NANC innervation of the rabbit internal anal sphincter. The study does not allow conclusions about the role of carbon monoxide, a recently proposed mediator of NANC responses in opossum internal anal sphincter.

Myocardial loss of glutamate after cold chemical cardioplegia and storage in isolated blood-perfused pig hearts.

Metabolic adaptation of the ischemic human heart includes release of lactate, augmented uptake of glucose and glutamate, together with increased release of citrate and alanine. In the present study exchanges of these metabolites were examined in relation to left ventricular function (LVF) in pig hearts during reperfusion after hypothermic cardioplegic-induced global ischemia and storage. Three groups of pig hearts were studied. Group I consisted of 11 hearts subjected to 9 minutes of warm ischemia prior to cold chemical cardioplegia with Bretschneider's cardioplegic solution (CCC), and hypothermic storage (HS), for a total of 180 minutes. Groups II and III, 8 hearts in each, were subjected to 90 and 180 minutes of CCC and HS, without precardioplegic warm ischemia. All hearts were reperfused in an isolated blood-perfused Langendorff model. Myocardial oxygen uptake and LVF were two-fold depressed in Group I compared to Groups II and III during the first 25 minutes of reperfusion. An increased uptake of glucose (p < 0.05) and augmented release of lactate (p < 0.01) and citrate (p < 0.001) were found during the reperfusion period in the hearts subjected to precardioplegic warm ischemia, indicating an increased total ischemic burden compared to Groups II and III. No significant changes in LVF or myocardial metabolism were noted between Groups II and III during reperfusion. In all three heart groups a substantial release or loss of glutamate was found at start of reperfusion, although in the preischemic state prior to cardioplegia pig hearts were found to extract glutamate from the circulation to an extent similar to that of the human heart.(ABSTRACT TRUNCATED AT 250 WORDS)

A possible role of the L-arginine-nitric oxide pathway in the modulation of cholinergic transmission in the guinea-pig taenia coli.

1. The role of the L-arginine-nitric oxide (NO) pathway for non-adrenergic, non-cholinergic (NANC) relaxation of the guinea-pig taenia coli was studied by recording isometric tension in response to transmural field stimulation (TMS). 2. In preparations precontracted with prostaglandin F2 alpha (PGF2 alpha, 10(-6) M), TMS induced frequency-dependent responses of the muscle strips which could be abolished by tetrodotoxin (10(-6) M). NG-nitro-L-arginine (L-NNA, 10(-4) M), an L-arginine analogue, and potent inhibitor of NO synthesis, stereospecifically inhibited maximum relaxations, but did not shift the frequency-response curve. Pre-incubation with NG-nitro-D-arginine (D-NNA, 10(-4) M), atropine (10(-6) M) plus L-NNA (10(-4) M), or atropine (10(-6) M) alone, had no influence on the frequency-response characteristics. 3. L-NNA (10(-7)-10(-4) M) concentration-dependently inhibited relaxations in PGF2 alpha (10(-6) M) precontracted strips in response to TMS, but did not abolish relaxations. Preincubation with L-arginine (10(-4) M) inhibited these effects of L-NNA. L-NNA (10(-4) M) had no effect on the inhibitory response during TMS in strips preincubated with atropine (10(-6) M). 4. The relaxation induced by sodium nitroprusside and forskolin (10(-9)-10(-4) M) was not influenced by L-NNA (10(-4) M) preincubation as expressed by identical pD2 and Emax values. 5. Contractions induced by PGF2 alpha (10(-9)-10(-4) M) and carbachol (10(-9)-10(-4) M) were not affected by pretreatment with L-NNA (10(-4) M), was expressed by identical pD2 and Emax values. 5. Contractions induced by PGFA (10-1- 10-4M) and carbachol (10-1 0-4 M) were not affected by pretreatment with L-NNA (10-4 M), as expressed by identical pD2 and Em. values.6. In conclusion, the L-arginine-NO pathway seems to play a role in the NANC innervation of the guinea-pig taenia coli. The inhibitory effect of NO or a NO-like compound depends on the integrity of the cholinergic pathways and it is proposed that this compound exerts its effects prejunctionally on cholinergic nerves, by inhibiting the release of acetylcholine.

Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter.

Circular muscle strips from opossum lower esophageal sphincter were suspended in organ baths for measurement of isometric tension. Nonadrenergic noncholinergic (NANC) inhibitory nerves were stimulated by means of transmural field stimulation. This induced frequency-dependent relaxations of the muscle strips. Methylene blue (3 x 10(-6) M; inhibits guanylate cyclase) and pyrogallol (10(-4) M; generates superoxide anions) had no influence on relaxations, whereas oxyhemoglobin [10(-5) M; binds nitric oxide (NO) and other nitroso compounds extracellularly] inhibited relaxations at all frequencies. NO concentration dependently relaxed the muscle strips. Pyrogallol (10(-4) M) and methylene blue (3 x 10(-6) M) inhibited and oxyhemoglobin (10(-5) M) nearly abolished relaxation induced by NO. S-nitroso-L-cysteine caused concentration-dependent relaxations of the muscle strips, which were inhibited by pyrogallol (10(-4) M), whereas methylene blue (3 x 10(-6) M) augmented the action of S-nitroso-L-cysteine. Methylene blue (3 x 10(-6) M) had no influence on the concentration-dependent relaxations caused by sodium nitroprusside (SNP). Oxyhemoglobin (10(-5) M), and to a lesser extent pyrogallol (10(-4) M), both inhibited the effects of SNP. The action profiles for S-nitroso-L-cysteine, NO, and SNP differed from the action profile for NANC nerve-mediated response. Although pyrogallol inhibited the effects of SNP, the action profile generally resembled the action profile for NANC responses more closely than did the profiles for S-nitroso-L-cysteine or NO. In conclusion, of the nitroso compounds studied, SNP most closely resembled the response to NANC nerve stimulation. Neither NO nor S-nitroso-L-cysteine individually mimicked the NANC response.

The role of the L-arginine-nitric oxide pathway in relaxation of the opossum lower oesophageal sphincter.

1. The role of the L-arginine-nitric oxide pathway in lower oesophageal sphincter (LOS) relaxation and oesophageal peristalsis was investigated. 2. Twenty four adult opossums were anaesthetized and the right vagus nerve was isolated in the neck and sectioned. Electrical stimulation, applied to the peripheral end of the nerve, resulted in a frequency-dependent relaxation of the LOS, and peristaltic and non-peristaltic contractions in the oesophageal body. 3. N omega-nitro-L-arginine (L-NNA, 10(-8)-10(-5) mol kg-1), an inhibitor of the L-arginine-nitric oxide pathway, inhibited LOS relaxation in a dose-dependent manner, but did not affect resting LOS pressure. At the highest dose of L-NNA no relaxation of the LOS was elicited in response to vagal stimulation. The effect of L-NNA, (10(-5) mol kg-1) was fully reversed by infusion of 10(-4) mol kg-1 L-arginine. Peristaltic velocity and amplitude of contractions in the oesophageal body were unaffected by L-NNA. 4. Infusion of sodium nitroprusside reduced LOS pressure to zero, and the drug was equally potent in control animals (-log ED50:8.1 +/- 0.2 mol kg-1) and in animals pretreated with L-NNA (-log ED50:8.2 +/- 0.3 mol kg-1). This suggests that the effect of L-NNA was not directly on guanylate cyclase. 5. A significant elevation of blood pressure was recorded after administration of L-NNA (10(-5) mol kg-1). 6. It is suggested that the L-arginine-nitric oxide pathway plays an important functional role for relaxation of the LOS, but not for oesophageal peristalsis. Whether the active substance is nitric oxide or a related nitroso-compound remains to be settled.

Thirty-day mortality after valve replacement for aortic stenosis over the last 22 years. A multivariate risk stratification.

Over the last 22 years (1965-86), the 30-day mortality rate (30-DMR) after valve replacement for primary or predominant aortic stenosis (AS, N = 690) fell from 20.0% for the first 100 consecutive patients, via 7.8% for the next 490, to 2.0% for the final 100 (P less than 0.0001). There was, however, a wide scatter in 30-DMR in the 11 consecutive 2-year periods, as well as during later years. The variation in 30-DMR was paralleled by changes in a high risk prognostic index (derived from a logistic regression model) and in a high coronary artery disease (CAD) score. In patients with a high CAD score who died within 30 days, 93% (N = 25) had CAD at autopsy compared with 37% (N = 11) of those with a low CAD score (P less than 0.0001). In 205 patients evaluated by coronary arteriography, the 30-DMR was 4.1% in 122 without CAD, 3.6% (3.8% for triple vessel/left main stem) for 55 with CAD who underwent bypass grafting, and 17.9% for 28 with CAD who did not have bypass grafting (P less than 0.0001). Left ventricular failure (LVF; episodes of pulmonary oedema and/or stasis), age, pronounced hypertrophy/strain in the ECG, and a high CAD score were independent incremental risk factors for 30-DMR. Quantitatively, LVF increased the risk 10 times more than pronounced hypertrophy/strain and a high CAD score. LVF also neutralized the influence of age. Modifying (symptom-masking) digitalis and/or diuretic treatment in functional class II patients (N = 189) increased the 30-DMR from 0.9% to 9.1% (P less than 0.01). The scatter of operative year-specific 30-DMR was related to changes in preoperative prognostic patient profiles and to unrevascularized CAD. Operative intervention in AS patients, even with discrete symptoms, and consistent revascularization of significant CAD, should be strongly advocated.

Twenty-two-year experience with aortic valve replacement. Starr-Edwards ball valves versus disc valves.

From 1965 through 1986, 817 patients underwent aortic valve replacement at our institution. Six hundred forty-five patients received Starr-Edwards ball valves, including 286 Silastic ball valves (Models 1200/1260), 165 cloth-covered caged-ball prostheses (Models 2300/2310/2320), and 194 track-valve prostheses (Model 2400). In contrast, 172 patients received disc-valve prostheses, including 126 St. Jude Medical aortic bi-leaflet disc valves, 32 Lillehei-Kaster pivoting disc valves, and 14 Björk-Shiley valves (6 convexoconcave and 8 monostrut). With respect to preoperative data, the 2 groups were comparable, with the following differences. The Starr-Edwards group included 1) more men (77% versus 51%; p < 0.0001); 2) a significantly older patient population (59 +/- 10 years versus 56 +/- 15 years; p < 0.0001); 3) more patients in New York Heart Association functional class III or IV (72% versus 65%; p < 0.01); 4) fewer patients with angina pectoris as a limiting symptom (20% versus 36%; p < 0.0001); and 5) patients who tended to receive larger prostheses (26 +/- 2 mm versus 23 +/- 3 mm, p < 0.0001). The overall 10-year survival rate +/- standard error was 59% +/- 2% for patients receiving Starr-Edwards valves and 63% +/- 6% for those with disc valves. The linearized complication rates (expressed as percentage per patient-year +/- standard error) for the Starr-Edwards and disc-valve groups, respectively, were 2.0% +/- 0.2% and 1.4% +/- 0.5% for thromboembolism, 2.1% +/- 0.2% and 3.9% +/- 0.8% for Coumadin-related hemorrhage, 0.5% +/- 0.1% and 0.3% +/- 0.2% for endocarditis, 0.3% +/- 0.1% and 0.7% +/- 0.3% for other prosthesis-related complications, and 4.8% +/- 0.1% and 6.4% +/- 1.0% for all complications together. There were no instances of thrombotic occlusion or mechanical failure. After the 6th postoperative year, no thromboembolic events were encountered in patients with a Silastic ball valve; the 15-year freedom from thromboembolic events was 89%. Cox regression analysis showed that 1) a prosthetic orifice diameter of 15 mm or less was associated with an increased mortality; 2) disc valves entailed an increased rate of hemorrhage and prosthesis-related complications considered as a whole; 3) and Lillehei-Kaster valves led to an increased rate of prosthesis-related complications other than thromboembolism, hemorrhage, and endocarditis. Neither the type of prosthesis nor the size influenced the rate of thromboembolism, endocarditis, or prosthesis replacement. Because of their proven durability and relatively low price, we advocate the continued use of Starr-Edwards Model 1260 Silastic ball valves that have an orifice diameter of 16 mm or more.

Valve replacement for calcified aortic stenosis in septuagenarians infers normal life-length.

Aortic valve replacement because of pure or predominant stenosis was performed in 1970-1986 on 101 patients aged 70-78 years, including 80 in NYHA function class III or IV. There were 16 deaths within 30 days, and coronary artery disease (unbypassed in all but 1 case) was found in 11 of the 13 with autopsy or preoperative arteriography. None of the 12 patients without significant coronary artery disease at angiography died perioperatively,but one of 12 with combined valve replacement and coronary artery bypass grafting died. Cumulative 1-year survival among the 101 patients/the 85 survivors of the first 30 days and/a normal population matched for sex, age and year of operation was 75/90/96%. Corresponding percentages for 5 years were 64/75/77, for 10 years 43/52/52, and for 15 years 35/42/27. Advanced disease with kidney failure or left ventricular end-diastolic pressure greater than 20 mmHg independently increased the overall mortality rate. The linearized rat of cerebral events (haemorrhage, embolism) was 2.7/100 patient years (age-specific background rate 1.6-1.9/100 patient years). The 30-day mortality among septuagenarians was reduced to 3% in 1988-1989 by routine revascularization in significant coronary artery disease. The patients who survived the first 30 days had normal life expectancy. Early operation may further improve the results.

Importance of the L-arginine-nitric oxide pathway in NANC nerve function of the opossum esophageal body.

Circular muscle strips from the opossum esophageal body obtained 3-5 cm above the esophagogastric junction were suspended in organ baths for measurement of isometric tension. Stimulation of nonadrenergic, noncholinergic (NANC) inhibitory nerves was performed using transmural field stimulation (TMS). During TMS, no mechanical response was elicited. After cessation of the stimulus a short period, also without mechanical response, intervened, and this period is called latency. The latency was followed by the 'off'-contraction. In control preparations, the latency and the amplitude of the 'off'-contraction were 1.47 +/- 0.17 s, and 3.8 +/- 0.9 mN, respectively. The inhibitor of the L-arginine-nitric oxide (NO) pathway, NG-nitro-L-arginine (L-NNA) concentration-dependently reduced the latency at concentrations greater than 10(-6) M (n = 6-7). At the highest concentration of L-NNA (10(-4) M), 'off' contractions were no longer seen. In 5 out of 7 preparations exposed to L-NNA (10(-4) M), a small contraction was seen during stimulation, and this contraction was abolished by atropine (10(-6) M) in all strips. L-NNA concentration-dependently reduced the amplitude of contractions at concentrations greater than 10(-6) M (n = 6-7). At 10(-4) M, the amplitude was reduced to 3 +/- 2% of that of the initial contraction. Preincubation with L-arginine (10(-5) M) had no influence on the latency. The effects of L-NNA on both latency and the amplitude of contraction were antagonized by preincubation with L-arginine (10(-5) M). Atropine (10(-6) M had no effect on the amplitude of the 'off'-contraction in control preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prosthesis-endocarditis in the aortic position in a 22-year case load. Surgical versus conservative treatment]. / Protese-endocarditis i aortaposition i et 22 års materiale. Kirurgisk kontra konservativ behandling.

During the period 1965-1986, a total of 852 patients underwent isolated aortic valve replacement. With 4,875 patients-years at risk, 24 patients developed prosthetic valve endocarditis (PE; 0.49% per patient-year). The five, ten and fifteen year cumulative freedoms from PE were 98.2%, 95.4% and 93.0%, respectively. PE was unrelated to pre- or intraoperative data. No patients submitted to operation for acute/subacute bacterial endocarditis of the native aortic valve developed PE. Out of the 12 episodes of PE within two years of the operation, seven (58%) were caused by Staphylococcus albus compared with two out of 12 (17%; p less than 0.05) subsequent episodes of PE. Seven of the nine infections with Staphylococcus albus were caused by a highly resistant nosocomial variant. Ten of the PE patients underwent replacement of the prosthesis while 14 were treated conservatively. The two therapeutic groups were comparable, although the surgically treated patients tended to be younger and to have more impaired cardiac status. All surgically treated patients and all patients treated conservatively and in whom post mortem verification was possible had paravalvular defects, annular abscesses and/or vegetations on the prosthesis. The thirty-day, one year and ten year cumulative survivals were 80%, 80% and 50%, respectively, after replacement of the prosthesis and 64%, 21% and 7%, respectively, after conservative treatment (p = 0.02). A Cox regression analysis identified conservative treatment, infection with Escherichia coli or Haemophilus influenzae and the need to intensify digitalis/diuretic treatment for congestive heart failure as independent risk factors. It is concluded that replacement of the prosthesis early in the course of the disease should be considered as the treatment of choice.

Valve replacement for aortic regurgitation: earlier operation may reduce the rate of late complications related to the prostheses.

Predictability of prosthesis- and sudden heart-related complications was examined in 121 patients who were alive 30 days after valve replacement (1965-86) for aortic regurgitation. A variety of prosthetic valves, mainly mechanical, were used. The Cox regression model was used to identify independent risk factors and to estimate the predicted freedom of events relative to combinations of these risk factors. In the following, linearized event-rates (LER) are given as number of events per 100 patient years +/- standard error. No risk factors could be identified for endocarditis (LER: 0.3 +/- 0.2) or anticoagulant-related hemorrhage (LER: 1.7 +/- 0.6). Only factors underlying deranged preoperative patient and heart status and cardioplegic method, but not the type of prosthetic valve, had predictive influence on the other complications. Predicted 10-year event-freedoms for low- versus high-risk estimate were 98% versus 46% for thromboembolism (LER: 2.1 +/- 0.6), 87% versus 68% for all prosthesis-related complications (LER: 5.0 +/- 0.8), 100% versus 0% for sudden heart-related events (LER: 2.0 +/- 0.5; myocardial infarction and arrhythmia), and 72% versus 38% for combined prosthesis- and sudden heart-related morbidity and mortality (LER: 7.0 +/- 1.0). By deciding to operate early in the course of aortic regurgitation, the rate of these complications may be "actively" reduced, and longevity and life quality of the patients improved.

The influence of coronary artery disease and bypass grafting on early and late survival after valve replacement for aortic stenosis.

The influence of coronary artery disease and bypass grafting on survival after valve replacement for aortic stenosis (1975 to 1986, N = 512) was analyzed. Mean follow-up for 30-day survivors was 5.1 years (0.1 to 12.9 years). A total of 205 patients had coronary angiography performed: 122 did not have coronary artery disease, 55 with coronary artery disease underwent bypass grafting, and 28 with coronary artery disease did not. Early mortality rates (less than or equal to 30 days)/5-year cumulative survivals (standard error) were 4.1%/86% (4%), 3.6%/68% (8%), and 17.9%/51% (13%), respectively (p less than 0.05/p less than 0.01). Triple vessel/left main stem disease was more prevalent in patients with coronary disease who underwent bypass grafting (47%) than in those who did not (14%; p less than 0.05). Multivariate analysis revealed that right ventricular failure and omission of bypass grafting in patients with coronary artery disease were independent determinants of early mortality. A Cox regression analysis identified coronary artery disease and aortic valve gradient as determinants of mortality after hospital dismissal, which was not influenced by bypass grafting. On the basis of a coronary artery disease score (positive predictive value for coronary artery disease of 66%) developed on the patients with angiography, 307 patients without angiography were divided into 234 with a low score and 73 with a high score. Early mortality rates/5-year survivals (standard error) were 6.4%/86% (2%) and 16.4%/67% (6%), respectively (p less than 0.01/p less than 0.001). Autopsy revealed stenotic or occlusive coronary artery disease in 92% of 12 early deaths in the group with a high coronary artery disease score and in 33% of 15 in the group with a low score (p less than 0.01). Left ventricular failure and a high coronary artery disease score were independent determinants of early mortality, whereas cardiothoracic index, a high coronary artery disease score, and left ventricular failure were independent predictors of death after hospital dismissal. Despite more severe coronary artery disease, bypass grafting reduced early mortality to a level comparable with that of patients without coronary artery disease, contrasting with a high early mortality rate for unbypassed coronary artery disease. Coronary artery disease increased the late mortality rate, which was not modified by bypass grafting. In the group without angiography, undiagnosed and unbypassed coronary artery disease probably increased both early and late mortality. Coronary angiography should be performed in all adult patients with aortic stenosis, and those with significant coronary artery disease should undergo bypass grafting concomitant with valve replacement.

Long-term prosthesis-related and sudden cardiac-related complications after valve replacement for aortic stenosis.

Predictability of prosthesis-related and sudden cardiac-related complications was examined in 630 patients who were alive 30 days after valve replacement (1965 to 1986) for aortic stenosis. Follow-up totaled 4,072 patient-years. A variety of prosthetic valves, mainly mechanical, were used. The Cox regression model was used to identify independent risk factors and to estimate predicted event-freedoms relative to combinations of these risk factors. There were no risk factors for endocarditis (0.5 +/- 0.1 [number of events per 100 patient-years +/- the standard error]). Except for "other" prosthesis-related complications (0.4 +/- 0.1), adversely influenced by porcine bioprostheses (n = 15) and by the Lillehei-Kaster prosthesis (n = 25), only factors underlying diseased preoperative patient/cardiac status had predictive influence. Predicted 10-year event-freedoms for low-risk versus high-risk estimate were 86% versus 73% for thromboembolism (1.7 +/- 0.2), 95% versus 32% for anticoagulant-related hemorrhage (2.4 +/- 0.2), 69% versus 36% for all prosthesis-related complications (5.0 +/- 0.4), 93% versus 0% for sudden cardiac-related events (myocardial infarction and arrhythmia) (1.8 +/- 0.2), and 66% versus 0.5% for combined prosthesis-related and sudden cardiac-related morbidity and mortality (6.8 +/- 0.4). In 193 patients with coronary arteriography, coronary artery disease was a significant risk factor for each of the complication modalities examined except other prosthesis-related complications, prosthesis replacement, and endocarditis. Deciding to operate early in the course of aortic stenosis might "actively" reduce the rate of these complications.

Long-term performance of Starr-Edwards silastic ball valves and St Jude Medical bi-leaflet valves. A comparative analysis of implantations during 1980-86 for aortic stenosis.

Long-term performance of Starr-Edwards silastic ball (SESB, n = 168) and St Jude Medical bi-leaflet (SJMB, n = 93) valves in patients who were alive 30 days after implantation (1980-86) for aortic stenosis was compared. Mean follow-up was 3.0 years (0.1-7.9 years). The SESB and SJMB groups differed as regards female gender (18% vs 47%, P less than 0.0001), NYHA classes III-IV (59% vs 72%, P less than 0.05), coronary artery disease (CAD, 32% vs 62%, P less than 0.01) in patients with coronary arteriography (n = 82 and n = 55, respectively), and prosthetic annulus diameter (26 +/- 1 vs 23 +/- 2 mm, P less than 0.0001). Five-year survival +/- SE in SESB vs SJMB patients was: total population, 89 +/- 3% vs 80 +/- 6% (NS); coronary arteriography population, no CAD, 90 +/- 4% vs 100% (NS), and with CAD, 71 +/- 11% vs 60 +/- 13% (NS; P = 0.01 for CAD). Five-year event-free survival +/- SE in SESB vs SJMB patients was 95 +/- 2% vs 97 +/- 2% (NS) for thromboembolism, 95 +/- 2% vs 89 +/- 4% (NS) for coumadin-related haemorrhage, 98 +/- 1% vs 99 +/- 1% (NS) for endocarditis, 98 +/- 1% vs 94 +/- 5% (NS) for paravalvular leak, 88 +/- 3% vs 79 +/- 6% (NS) for all valve-related complications, and 98 +/- 1% vs 95 +/- 4% (NS) for prosthesis replacement. Thrombotic occlusion or structural failure were not observed. No patients without CAD experienced thromboembolic events. Cox regression analyses (in both total population and coronary arteriography population) of survival as well as the various complications revealed that the type of prosthesis did not have predictive influence. CAD was an independent risk factor for thromboembolism, haemorrhage, and all valve-related complications. Previous systemic hypertension was independently predictive of haemorrhage. The SESB and SJMB prostheses showed comparable and acceptable long-term performance. Only patient-related variables, notably CAD, influenced late results. The proven durability and relatively low price of the SESB valves together with the excellent haemodynamic performance of even small-sized SJMB valves should be considered in the light of the present results.

Recovery after cold cardioplegic arrest of isolated blood-perfused hearts excised from non-anesthetized pigs.

An isolated blood-perfused pig heart model has been established in order to evaluate the recovery of hearts obtained from slaughterhouse domestic pigs avoiding anesthesia and direct experiments on animals. Eleven hearts subjected to 9 min of normothermic ischemia were infused with cold modified Bretschneider solution. After 180 min of cardioplegic-induced global ischemia (including 9 min of normothermic ischemia) 8 hearts were reperfused for 120 min. Left ventricular function (measured isovolumetrically by means of a balloon, and expressed as developed left ventricular pressure, positive and negative dP/dt) was stable during the whole reperfusion period. Lactate production was abolished after 25 min of reperfusion, while there was a small glucose extraction during the whole reperfusion period. Slight deterioration of the mitochondria was found during the induced cardiac arrest, however, reversing during the reperfusion. Thus, due to the stability of left ventricular function, improved metabolism and ultrastructure during the reperfusion period, the model with no use of laboratory animals, and without any influence of anesthesia, seems to be suitable for testing the pure effect on the performance of the left ventricle of drugs and substrates added to the reperfusate during the reperfusion period.

Early and late prognosis after valve replacement in aortic regurgitation. Preoperative risk stratification and reasons for a more aggressive surgical approach.

From 1965 through 1986 136 patients underwent valve replacement for aortic regurgitation. Mean age was 50 years and male:female ratio 3.7:1. Hospital mortality (HM, less than or equal to 30 days) varied with NYHA classes and digitalis/diuretics treatment (D/D):I (n = 80) 0%, II without D/D (n = 17) 0%, II with D/D (n = 21) 5%, III (n = 55) 7%; and IV (n = 35) 29% (p less than 0.01). Long-term survival was examined for 121 patients who were alive 30 days postoperatively. Five- and 10-year cumulative survival +/- SE were 80 +/- 4% and 66 +/- 6%, respectively. No late deaths were noted for NYHA class I and NYHA class II without D/D; NYHA class II with D/D had survival characteristics comparable to NYHA class III with 10-year survivals of 60%. Patients with acute regurgitation (endocarditis, n = 35) had a 10-year survival +/- SE of 88 +/- 5% compared to 57 +/- 7% for chronic regurgitation (p = 0.05). A Cox regression analysis revealed that ventricular ectopic beats, chronic regurgitation, left ventricular failure, and right ventricular failure were independent risk factors. Presence and different combination of these risk factors identified 5 risk groups (A-E) with 10-year survivals of:A (n = 16) 100%; B (n = 50) 75%; C (n = 37) 63%; D (n = 15) 27%; and E (n = 3) 0% (p less than 0.0001). Minimally symptomatic patients without preoperative medical treatment for congestive heart failure had superior survival characteristics compared to those who received treatment.(ABSTRACT TRUNCATED AT 250 WORDS)