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Hemolysis in total artificial heart (TAH) recipients was analyzed. From a total of 66 long-term experiments lasting from 30-314 days performed in the Brno Research Center, in 53 animals, the total red blood cell (RBC) count, hematocrit, total hemoglobin, and free plasma hemoglobin were investigated. We could essentially divide the whole group of calves in 2 subgroups. The first subgroup was calves with hemolytic reactions, and the second subgroup was calves without any hemolytic reaction at all. In the first subgroup, hemolysis occurred in 47% of the overall number of animals during extracorporeal circulation (ECC), in 15% during ECC and later periodically during the experiment, in 8% during ECC and then continuously during the experiment, and finally in 10% not during ECC but repeatedly during the experiment. In 20% of the animals from the overall number, hemolysis did not occur at all (second subgroup). These results testify to the great individual differences within 1 breed (Bohemian with a substantial component of Holstein). These differences are further modified by exogenous and endogenous factors. First, the inborn resistance of the RBC membrane and also thrombi formation and the mineralization of the driving diaphragm are very important. The extreme situation of decreased RBC membrane resistance was proved using a calf from another breed, the slow growing Scottish Highland breed, which did not survive 22 days of pumping due to intractable lethal hemolysis. These factors are also indicated by the hemolytic action of some drugs (e.g., Dopegyt) used during the experiment for another reason. Also important are the mechanical forces of pumping, surface moieties of the biomaterial, mineralization of the driving diaphragms, thrombi formation, infection, etc. Essentially, the hemolytic reaction in the TAH recipient has a multifactorial character. Hemolysis is undoubtedly an important factor, which can have a profound impact on the length of survival. The experimental and clinical experiences must be continuously integrated, and conclusions valid for human TAH application must be considered as very important for further TAH experimental and clinical research.

Twelve total artificial heart (TAH) models have been developed at the Brno Research Center. Devices VII, VIII, and IX were constructed on the principle of asymmetry. Three main objectives had to be fulfilled by this construction. First, contact of the flap inflow valve with the diaphragm during the pumping cycle had to be avoided. Second, the evacuation regimen of the blood chamber needed to be improved. Third, the danger of thrombi formation due to the lesser incidence of the dead corners had to be decreased or eliminated. The type VII heart has a roof-shaped polyurethane valve in the outflow tract whereas the type VIII heart has a flap valve. The decrease of thrombi incidence around the outflow valve was thus secured, and the driving pressure was decreased as well. In the type IX heart, the small additional flap valve is attached to the outflow valve. In one Brno VII device, Imachi's jellyfish valve has been mounted. Altogether, 62 long-term experiments with survival times of 30-314 days have been performed. To this number, 4 comparative experiments using the Rostock artificial heart were added.

A driving diaphragm in the long-term working total artificial heart (TAH) is under serious mechanical stress, and the long steady contact with blood causes changes to the diaphragm's surface. These changes can be influenced either by local or systemic interventions. In our study, we tried to follow the development of changes to the diaphragm's surface comparing the samples of diaphragms of long (over 30 days) and short (under 30 days) surviving calves and the effect of some preventive measures as well. We could confirm the presence of two types of calcification: a dystrophic calcification affecting primarily formed thrombi and necrotic tissue, and a primary type of calcification that begins in the form of calcifying nuclei on the protein layer of the polyurethane surface that is later on extensively covered with a fibrin network and blood cells. The calcified deposits caused mechanical damage or were the source of microembolization to the vital organs. A clotting mechanism occurs at the same time as the calcifying process from the beginning, often forming a fibrin network in and over the calcified deposits. An attempt at prevention was made by systemic administration of colloidal iron solution, Ferrum Lek (ferri saccharate in a stable colloidal form), based on the concept of the so-called reversed calciphylaxis.

The technical aspects of artificialheart design for experiments on calves are presented in this paper. The object of the design was to verify the basic anatomic and hemodynamic criteria for the design of more perfect cardiac prostheses. Each of the ventricles has a 100-ml stroke volume and is dismountable. Rigid parts are made of polymethylmethacrylate. The inlet valve has the shape of a flap. The outlet valve has two polyurethane reinforcing leaves. The diaphragm is also made of polyurethane. During tests using artificial circulation, a maximum cardiac output of 14.6 L/min was achieved. Typical sensitivity of flow on the atrial pressure is 0.3 L/min/torr at a frequency of 90 pulses per minute.

Hemodynamic analysis was carried out during long-term experiments with the pneumatic total artificial hearts TNS-BRNO-II and TNS-BRNO-III to determine standard methods of starting artificial hearts and criteria for their long-term operation in vivo. In long-term experiments, regulatory mechanisms automatically regulating the systole length and diastolic aspiration pressure have also been verified. Comparison of hemodynamic variables obtained from invasive measurements with pneumatic pressure curves permitted the control and monitoring of the experiment in its entirety by noninvasive methods only. The control of the artificial heart using the Chirasist TN 3 and Chirasist TN 4 was adapted to specific properties of the pumps, above all to the functions of the atypical inlet valves. The terminal stages of the experiments have shown that a 100-ml pump can ensure survival of experimental calves up to 210 kg body weight.

An indication chamber, inserted between the right heart drive and the pump proper, was designed to provide continual measurement of the quantity of blood pumped by the pneumatic artificial heart. The flow is evaluated from the motion of a piston provided with a photoelectric transducer. The effect of compressibility of the drive gas on measurement accuracy is eliminated. The indication chamber provides for automatic replenishment of gas that escapes by diffusion and through minor leakage. During testing in an artificial circulation within the range of physiological conditions, measurement in accuracies did not exceed 5%.

Over the last 2 1/2 years, eight calves with implanted total artificial hearts (from experimental group IV) have survived for greater than 1 month. In this group two subgroups were further differentiated, subgroup IVa, including three calves surviving 31, 35, and 75 days, and subgroup IVb, with five calves surviving 104, 142, 150, and 155 days and one calf still surviving greater than 160 days. Mean survival in the fourth group was greater than 106.5 days. The artificial ventricles used were the TNS-BRNO-II made of polymethylmethacrylate (seven calves) and the TNS-BRNO-III, made of segmented polyetherurethane (one calf). The controller and driving units were of our own design. The Chirasist-TN-3 and TN-4 worked without trouble over the total duration of the studies in all calves. Autoregulation of suction was used in three of these calves. All calves survived in good physiological condition; however, some common changes were observed in all of them, such as a gradual central venous pressure increase and liver enlargement. Anticoagulation therapy was used in all calves. Causes of death were technical in three cases and biological in four. Body weight gains were normal in the majority of these calves, with slight individual differences observed. Diaphragm mineralization of various degrees was observed in three cases. In one of them it was directly related to the cause of death. These results are very encouraging for further development of the total artificial heart research in our center.