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.

Chronic heart failure induced by multiple sequential coronary microembolization in sheep.

OBJECTIVE: Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We aimed to establish a stable and reproducible animal model of chronic heart failure in sheep. METHODS: Sheep (n=8, 77 +/- 4 kg) were anesthesized and a 5F sheath was implanted into the left carotid artery. The left main coronary artery was catheterized under flouroscopic guidance and bolus injection of polysterol microspheres (90 microm, n=25.000) was performed. Microembolization (ME) was repeated up to three times in two to three week intervals until animals started to develop stable clinical signs of heart failure. Clinical and echocardiographic data were analyzed at baseline (base) and at three months (3 mo) after first ME. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. Another four healthy sheep (79+/-6 kg) served as control animals. RESULTS: All animals developed clinical signs of heart failure as indicated by increased heart rate at rest (68+/-4 bpm (base) to 93 +/- 5 bpm (3 mo) (p<0.05)), increased respiratory rate at rest (28+/-5 (base) to 38 +/- 7 (3 mo) (p<0.05)) and increased body weight 77 +/- 2 kg to 81 +/- 2 kg (p<0.05) due to pleural effusion, peripheral edema and ascites. Echocardiographic evaluation revealed significantly an increase of left ventricular enddiastolic diameter from 46 +/- 3 mm (base) to 61 +/- 4 mm (3 mo) (p<0.05). Clinically and echocardiographically no significant changes were revealed in healthy control animals. CONCLUSIONS: We conclude that multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and echocardiographical signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, e.g. for studying the impact of mechanical unloading, mechanisms of recovery and reverse remodeling.

[Josef Koncz (1916-1988)--pioneer of cardiac surgery]. / Josef Koncz (1916-1988)--Pionier der Herzchirurgie.

Josef Koncz (1916-1988) was until given emeritus status in 1982 director of the Department of Cardiothoracic and Vascular Surgery, which was specifically founded for him in Goettingen, Germany. By the fusion of three different surgical branches the University hospital of Goettingen took over the role of a pacemaker and initiated a standard in the development of this new specialty in Germany. The scientific and clinical work done by the Department of Cardiothoracic and Vascular Surgery was shaped by the personality of the surgeon and scientist Josef Koncz. He was a successful surgeon and innovative pioneer in one person. Already in 1956, he started open-heart surgery and proceeded this technique in an impressing series. In 1965 he was the first in Germany who operated upon the transposition of the great vessels by Mustard's method and developed together with his long-standing assistant, Huschang Rastan, an operation technique to extend the left-ventricular outflow tract combined with tunnel-shaped subvalvular aortic valve stenosis. Another essential element of his work is related to the establishment of the Cardiothoracic and Vascular Surgery as an independent specialty, ending in the foundation of the German Society for Thoracic and Cardiovascular Surgery in 1971.