Free skeletal muscle transplantation to an infarction area: an experimental study in the dog.

In plastic surgery, free skeletal muscle flaps are used for treatment of non-healing injuries like chronic osteitis or radiation ulcers. We wanted to evaluate if the neoangiogenesis induced by these flaps can also constitute a method for revascularization in ischemic heart disease. In diffuse small vessel coronary heart disease, patients are not suitable for bypass surgery because it is impossible to create a microanastomosis with the coronary artery. As an alternative, a free striated muscle flap, transplanted onto the heart, can constitute a source of neovessels. With the induction of extra-intracardial collaterals that develop within 4 weeks after transplantation of the flap, a new surgical approach may be offered to those patients. Our experimental work was performed with 20 dogs. In these, a myocardial infarction of the anterior wall was selectively produced using the Judkins-technique (Radiology 89: 815-824, 1967) for injection of Sephadex-microspheres. Four weeks later a free pectoralis muscle flap was transplanted onto the anterior wall of the heart. Arterial blood supply was achieved with an anastomosis with the internal mammary artery. The venous flow was directed into the right atrium. Four to eight weeks after surgery, the patency of the anastomosis was studied by angiography, showing patency in almost all surviving animals. Histological examination of the hearts revealed a prominent vascular network penetrating into the underlying myocardium. Corrosion cast preparations, as well as a postmortem angiography, showed even further penetration of the neovessels into the uninjured parts of the myocardium. Thus, myocardial revascularization may be achieved by transplantation of a skeletal muscle onto the heart.

[Myocardial revascularization with a free skeletal muscle transplant--a functional analysis of angiogenesis]. / Myokardrevaskularisation durch ein freies Skelettmuskeltransplantat--eine Funktionsanalyse der Angiogenese.

In order to evaluate the functional aspect of myocardial neovascularization after grafting a free skeletal muscle flap onto the heart in the dog with an arterial anastomosis to the internal mammary artery (IMA), a gradual occlusion of the left anterior descending coronary (LAD) was induced. This was achieved implanting an Ameroidconstrictor on the LAD, that due to its hygroscopical material induces a gradual coronary occlusion. The occlusion of the LAD was angiographically confirmed in vivo. In one dog the selective angiographical demonstration of the IMA anastomosed to the graft was achieved. This showed retrograde filling of the LAD occluded by the Ameroidconstrictor. These findings were confirmed in all dogs by a microvascular corrosion cast preparation of the vasculature induced from the graft, that was differentiated from the coronaries by a different coloured casting material. The occluded LAD was filled in all preparations by the casting material applied into the IMA. Thus, grafting of a free skeletal muscle flap anastomosed to the IMA onto the dog's heart produces a functional myocardial neovascularization.

A microcorrosion cast study for analyzing a new method of indirect myocardial revascularization.

In order to study the process of angiogenesis a free skeletal muscle flap was transplanted onto the myocardium of the dog. A microvascular anastomosis with the internal mammary artery (IMA) provided the blood flow to the free graft. In 6 dogs, a myocardial infarction of the anterior wall was induced in order to produce a tissue injury. Four weeks later the skeletal muscle flap was transplanted onto the area of infarction in two dogs with its pars anterior in contact with the heart. In two dogs, the muscle was grafted with its pars posterior, i.e. the muscle fascia between the heart and the graft. In two other dogs, the flap was transplanted with its pars anterior in contact with the heart onto a healthy myocardium. Two animals with infarction were left as controls. Eighteen weeks later a microcorrosion cast was prepared from the hearts with the muscle flap. This evidenced neoangiogenesis in the heart only after transplantation of the graft with its pars anterior onto the myocardium whether it was ischemic or not. The intact muscle fascia, though, inhibited sprouting of vessels. In the controls no angiogenic activity was noted. Results are discussed with regard to the probable origin of the neovessels.

Cardiac arrhythmias during experimental induction and management of myocardial infarction in the dog.

The experimental production of a myocardial infarction (MI) in the dog was achieved adopting a new catheter technique. After induction of the MI, a variety of arrhythmias appeared and were classified according to the Lown-classification as more or less severe. The therapy was achieved with antiarrhythmics class 1-111 (Vaughn-Williams classification) for late premature ventricular beats or couplets. Sinus tachycardia was often terminated by occular or sinus carotis pressure or a new selective sinus blocking agent. Results showed Amiodarone to be the drug of choice in the treatment of severe arrhythmias (Lown IV and V) like triplets or salves of extrasystolies. Ventricular fibrillation always resulted in the death of the animal, because fibrillation was not convertible by direct current cardioversion, endovenous injection of Lidocaine or even internal cardiac massage. The registration of hemodynamic parameters (left ventricular end diastolic pressure, wedge pressure, pulmonary and aortic pressure) was shown to be important in controlling the therapy, as well as blood gas and electrolyte analysis.

Cardiomyoplasty to improve myocardial collateral blood supply as an alternative to transplantation in intractable angina.

In diffuse small-vessel coronary heart disease, heart transplantation may be indicated for intractable angina. As an alternative, a free striated muscle flap can constitute a source of neovessels. Those extraintracardial collaterals develop only 4 weeks after transplantation of the flap as shown by the following experiments with seven dogs. In those animals a myocardial infarction of the anterior wall was selectively produced by the Judkins technique for the injection of Sephadex microspheres. Four weeks later a free pectoralis muscle flap was transplanted onto the anterior wall of the heart. Arterial blood supply was achieved by anastomosis with the internal mammary artery. The venous flow was directed into the right atrium. Six weeks after surgery the patency of the anastomosis was studied by angiography, which showed patency in all animals. Pathologic examination of the hearts revealed a prominent capillary network penetrating into the underlying myocardium. Corrosion cast preparations showed even further penetration of the capillary network into the noninjured parts of the myocardium. Thus myocardial revascularization could be achieved by transplantation of a skeletal muscle on the heart.

A cardiac assist device as blood supply in ischemic heart disease.

Before the event of modern bypass surgery revascularisation of the heart was tried with the transplantation of pedicled muscle flaps onto the heart. For patients who cannot undergo bypass surgery this method could be--in a modified way--of help. This was shown in 12 dogs. In those a free muscle flap was transplanted onto the heart which had undergone a previous artificial infarction. The muscle flap was anastomosed with the a. mammaria, venous flow was directed into the right atrium. After 5 months the muscle was almost completely atrophic, but a fit capillary network was penetrating the underlying myocardium.

Experimental selective myocardial infarction in the dog without open-chest-surgery.

In 16 dogs, a selective myocardial infarction (MI) was experimentally provoked without open-chest-surgery by means of microspheres (MS) injected into a Judkins-catheter positioned into the left anterior descending coronary (LAD) under fluoroscopy. This was shown by ECG-abnormalities, increase of the serum-enzymes of myocardial necrosis, decrease of left ventricular end diastolic pressure (LVEDP), wedge pressure, and cardiac output. After 5 weeks, thoracotomy showed a myocardial infarction limited to the anterior wall of the heart, which was of subendocardial location and consisted of multiple zones of microinfarction. Histological examination of the corresponding area showed necrosis of myocardial muscle fibres.

[Neo-angiogenesis after transplantation of a free skeletal muscle flap to the myocardium of the dog]. / Neoangiogenese nach Transplantation eines freien Skelettmuskellappens auf das Myokard des Hundes.

For the study of the process of neovascularization the effects of the transplantation of a free skeletal muscle flap on the heart of the dog were studied. For this purpose, in 14 mongrel dogs a myocardial infarction of the anterior wall of the heart was produced by the selective injection of microspheres into the left anterior descending artery. In 12 of those, on the area of infarction 4 weeks later a free pectoralis muscle flap was transplanted with its pars anterior in contact with the myocardium (group A). The arterial anastomosis was achieved with the internal mammary artery, the venous flow directed into the right atrium. In 2 other dogs (group B) the pectoralis flap was transplanted with irt pars anterior on a healthy myocardium. In 2 further dogs (group C) the pectoralis flap was transplanted on a infarcted myocardium with its pars posterior, i.e. the muscle fascia interponed. 16 weeks later a microcorrosion-cast-preparation and histological examinations showed in group A and B a prominent capillary network penetrating from the muscle into the myocardium, whereas in group C the muscle fascia inhibited this process. Thus, for the process of neovascularization the "bloody" contact between a skeletal muscle graft and the myocardium is necessary. Results are discussed with regard to possible factors inducing neoangiogenesis.