Histological changes in a model of chronic heart failure induced by multiple sequential coronary microembolization in sheep.

AIM: Valuable models of chronic heart failure to perform histological studies are scarce. The authors aimed at investigating histological changes of the heart, lung, liver and kidneys in a stable and reproducible animal model of chronic heart failure in sheep. METHODS: In 8 sheep (N.=8, 77+/-2 kg) chronic heart failure was induced by multiple sequential microembolization through bolus injection of polysterol microspheres (90 microm, N=25 000) into the left main coronary artery. Microembolization (ME) was repeated up to three times in two to three week intervals until animals started to develop stable signs of heart failure. Therefore, clinical and hemodynamic parameters were measured (Troponin T, heart and respiratory rate, cardiac output) after each embolization. Clinical examination was carried out by a veterinarian. All animals were followed for 3 months after first microembolization and then euthanized for histological examination. Histological data of the heart, lung, liver and the kidneys were analyzed in hematoxylin-eosin (HE) stains (10x, 25x, 100x) at baseline (control group) and at 3 months after first ME. Additionally preparations of heart tissue were stained with Picro-Sirius-Red (PSR) for planimetric quantification. A score from 0 to 4 according to Rassler et al. (2005) was used to assess the degree of lung injury. RESULTS: All animals developed histological signs of heart failure as indicated by island-like, patchy fibrosis of the heart. Planimetric quantification (PSR stain) of the heart revealed a significant increase of the total amount of fibrosis from 8+/-2% (base) to 21+/-4% (3 months) (P<0.05), which was distributed homogeneously throughout the left ventricle (20+/-3% left ventricular [LV] anterior wall, 21+/-4% LV posterior wall, 20+/-4% septum). Histologic analysis of the lung demonstrated a moderate degree of interstitial edema and pronounced peribronchial processes of inflammation with beginning proliferation of fibrotic tissue. Liver tissue showed histological changes in terms of pericentral adiposis as sign of hypoxia in course of lacking perfusion. Signs of liver congestion could be detected histological in form of central-venous accumulation of erythrocytes and dissolution of liver tissue in proximity of the central veins. Kidney preparations illustrated loss of endothelial function and vascular occlusions, caused by microspheres, with decline of renal parenchyma particularly of the tubules. CONCLUSION: Multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with histological signs of chronic ischemic cardiomyopathy and pathological changes of lung, liver and kidney, which can directly be coursed by chronic heart failure. Thus, the present model may be suitable in experimental work on heart failure and LV assist devices, e.g. for studying the impact of mechanical unloading, mechanisms of recovery and reverse remodeling.

Combined mitral valve and coronary artery surgery: ischemic versus non-ischemic mitral valve disease.

OBJECTIVES: Mitral valve combined with coronary artery surgery is associated with a higher hospital mortality than each operation in particular. Controversy exists regarding the predictive value of ischemic mitral valve disease (MVD) on outcome. METHODS: Between 1984 and 1997, 262 patients underwent mitral valve operations (replacement, n = 198; repair, n = 64) in combination with coronary revascularization. The etiology of MVD was secondary to ischemic heart disease (group I) in 82 (31%) patients, and non-ischemic (group II) in 180 (69%) patients (rheumatic, 139 patients (53%); degenerative, 41 patients (16%)). Both groups were similar in age, cardiac risk factors and pulmonary artery pressure. Patients of group I had significantly more severe coronary artery disease, more often an impaired left ventricle and myocardial infarction, and were in a worse functional condition. The mean number of bypass grafts was significantly higher in group I. The follow-up was 98% (230/234 patients). RESULTS: With 19.5%, the hospital mortality was significantly increased in group I compared with 6.7% in group II (P = 0.002; overall, 10.7%). Mitral valve repair or replacement had no influence on early outcome, although mitral valve repair was performed more often in group I (37 versus 19%). The survival (valve-related event-free survival) after discharge from hospital in the 1st, 5th and 10th year was 94 (94%), 70 (66%) and 53% (35%) in group I and 96 (95%), 79 (76%) and 54% (41%) in group II, respectively. The long-term functional capacity was equally good in both groups (New York Heart Association mean, 1.86 versus 1.72). CONCLUSIONS: Patients with ischemic MVD are in a worse cardiac condition with significantly higher hospital mortality than patients with non-ischemic MVD and coronary artery bypass grafting. Once discharged from hospital, both groups have comparable long-term outcomes, with the best results in patients with degenerative MVD.

[Risk assessment of mitral valve surgery combined with myocardial revascularization]. / Valoración del riesgo de la cirugía mitral combinada con la revascularización miocárdica.

INTRODUCTION AND OBJECTIVES: Patients with combined mitral valve operation and coronary artery surgery represent a high risk group. The aim of this retrospective study was to evaluate which factors affect early and late postoperative results in this particular group of considered high risk patients. PATIENTS AND METHOD. Between 1984 and 1997, 264 patients (mean age: 63 +/- 7.3 years) underwent mitral valve surgery (199 patients; 75% mitral valve replacement, 25% mitral valve repair) in combination with coronary revascularization (mean 2.4 +/- 1.3 grafts). Follow-up comprised a mean of 69 +/- 42 months and was 98.3% complete. RESULTS: Early mortality was 10.6% (28/264). Ischemic mitral regurgitation operated on in emergent status, moderate to severe reduced left ventricular function and advanced age (> 60 years) were independently associated with early hospital mortality (p < 0.05). Ischemic etiology of mitral valve disease (emergency and elective operations), severity of mitral regurgitation and New York Heart Association (NYHA) functional class IV were related to early hospital mortality, only with univariate statistics. Actuarial survival was 86, 69 and 48% at 1, 5 and 10 years, respectively. The preoperative NYHA functional class was the only variable independently related to late survival. Eighty-five percent of the surviving patients were in NYHA functional class I and II. CONCLUSIONS: Mitral valve operation combined with coronary artery bypass grafting is associated with a high early hospital mortality. Independent risk factors of early mortality are emergency operation of ischemic mitral valve disease, reduced left ventricular function and advanced age. Long term survival is independently influenced only by preoperative NYHA functional class IV.

Surgical therapy of fulminant pulmonary embolism: early and late results.

BACKGROUND: Pulmonary embolectomy remains the only option for patients with fulminant pulmonary embolism and failure or contraindication of thrombolysis even today. Increasing prevalence of heparin-induced thrombocytopenia type II (HIT) adds a new significant problem, which was investigated in a retrospective study. METHODS: Between 1/1979 and 1/1998 41 patients (21 male; age: 51.1 +/- 14.8 years) with fulminant pulmonary embolism underwent pulmonary embolectomy under cardiopulmonary bypass: group I (1979-89): 31 patients; group II (1990-98): 10 patients. Group II included only patients who did not meet the criteria for acute thrombolysis, in 4 patients a HIT was preoperatively assured. All patients were in strongly compromised hemodynamic condition (33/41 high-dose catecholamines, 24/41 mechanical ventilation, 14/41 preoperative cardiopulmonary resuscitation). RESULTS: Perioperative mortality was 29% (group I: 9/31; group II: 3/10; n.s.) Preoperative resuscitation was the only predictive factor (with resuscitation: 9/14; without resuscitation: 3/27; p < 0.001). Severe but not fatal complications occurred in 11 patients: they fully recovered following treatment. Follow-up was completed to 93% (281 patient-years; mean: 10.6 years) and discovered 5 late deaths (late mortality: 1.7%/patient-year; 1 patient: bleeding due to anticoagulation; 4 patients: not related to operation). 26/28 (93%) patients were in NYHA functional class I or II. No recurrent pulmonary embolism or late clinical symptoms related to embolectomy were observed. There was no difference between group I and group II (including the 4 patients with HIT) regarding perioperative mortality, complication, and late results. CONCLUSIONS: Pulmonary embolectomy on cardiopulmonary bypass remains an adequate therapy in patients with failure of or contraindication to thrombolysis, and HIT is not a contraindication.

Hypoxic Hypoperfusion Fails to Induce Myocardial Hibernation in Anesthetized Swine.

BACKGROUND: Congenital origin of the left coronary artery from the pulmonary artery (ALCAPA) results in chronically dysfunctional myocardium with the partial ability to recover after revascularization. We attempted to establish an ALCAPA syndrome in anesthetized pigs for 24 hours and to compare it with stunned and infarcted myocardium. METHODS AND RESULTS: In group 1 (n = 12), a bypass graft was interposed between the pulmonary artery and the left anterior descending coronary artery (LAD). Reduction of flow in the LAD with gradual increases in flow from the pulmonary artery resulted in an incremental reduction of segment shortening (8.9 +/- 5.3% at 24 hours vs 26.6 +/- 10% at baseline, P <.005). In group 3 (n = 5), 2 cycles of 10-minute LAD occlusion resulted in decreased segment shortening with slow recovery (at 24 hours 18.7 +/- 1.3% vs 24.2 +/- 4% at baseline, segment shortening with slow recovery (at 24 hours 18.7 +/- 1.3% vs 24.2 +/- 4% at baseline, P <.05). In group 3 (n = 6), 1-hour LAD occlusion reduced segment shortening at 24 hours to 4.7 +/- 5.2% (P <.005 vs baseline). Histological analysis of the LAD territory revealed severe degeneration, myolysis, and alteration of the chromatin structure in group 1 comparable to ischemic cell death in group 3, whereas control areas and the LAD area in group 2 showed only minor structural alterations. Infarct size/risk area, as measured by tetrazolium staining, was 49.8 +/- 11.2% in group 1, 9.3 +/- 8.1% in group 2 (P <.005), and 60.3 +/- 9% in group 3. CONCLUSION: Hypoxic myocardial hypoperfusion from the pulmonary artery results in myocardial necrosis in anesthetized pigs. These findings are in contrast to the concept of myocardial hibernation in the ALCAPA syndrome because in this model, hypoxic hypoperfusion failed to induce adaptation to preserve myocardial structure.

Pulmonary embolectomy: review of a 15-year experience and role in the age of thrombolytic therapy.

OBJECTIVE: Surgical intervention for fulminant pulmonary embolism is nowadays most commonly restricted to patients with failure of or contraindication to thrombolytic therapy. Such a second choice indication may alter operative risks or late outcome, and this was investigated in a retrospective study. MATERIAL AND METHODS: Thirty-six patients (17 male, mean age: 50.6 +/- 15.5 years) with fulminant pulmonary embolism of either the pulmonary trunk or one of the pulmonary arteries and at least one contralateral segment underwent pulmonary embolectomy on cardiopulmonary bypass during a 15-year period (1979-89: 31 patients, group I; 1990-94: 5 patients, group II). Group II included only patients who did not meet the criteria for acute thrombolysis. All patients were in strongly compromised circulatory conditions (29/36 high dose catecholamines, 20/36 mechanical ventilation, 14/36 pre-operative cardiopulmonary resuscitation). RESULTS: The perioperative mortality rate was 26% in group I (8/31 patients, 7 with pre-operative cardiac arrest) and 20% in group II (1/5 patients not related to failure of previous thrombolytic therapy). Severe but non-fatal complications occurred in six patients who fully recovered following treatment. Follow-up was completed to 93% (25/27 patients) and comprised a total of 248 patient-years (mean: 119 months). Twenty-three out of 25 patients (92%) were in functional class I or II (NYHA). No recurrent pulmonary embolism or late clinical symptoms related to embolectomy were observed. One patient died 8 years postoperatively (late mortality: 0.4% patient-year). There was no difference between group I and group II regarding perioperative mortality, complications and late results. CONCLUSIONS: Late results after pulmonary embolectomy are excellent in respect to functional class and late mortality. Early mortality is closely associated with preoperative cardiac arrest. Previous thrombolysis does not alter the perioperative risks, occurrence of complications or late outcome after surgical intervention.