To prove whether the interaction between insertion/deletion (I/D) angiotensin I converting enzyme (ACE) and M235T angiotensinogen (AGT) gene polymorphic alleles could contribute to causing essential hypertension, we examined subjects from the Czech Republic (365 Caucasians total; 202 normotensives and 163 hypertensives). Subjects were genotyped for insertion/deletion polymorphism of ACE (I/D ACE, intron 16) and for M235T polymorphism of angiotensinogen gene (AGT, exon 2) by means of the polymerase chain reaction (PCR) method. The case-control approach was used. Fisher's exact test followed by Holmes's test to overcome the problem of multiple comparisons were used for the statistical analysis of data. No association of single gene allelic variants with essential hypertension was found in our population. Having compared only double homozygote combinations, the association of the DDMM genotype with essential hypertension was proven (P = 0.0081). To the contrary, IITT (P = 0.0086) was found more frequently in normotensive subjects. We conclude that the interaction of the I/D ACE and M235T AGT polymorphic alleles can contribute to essential hypertension, despite the absence of single gene associations with the condition.
Evaluation of five longest surviving calves among a total of 54 longterm survivors, at the Brno Research Centre was performed. These calves were treated by administration of antihypertensives and partially by electrical stimulation of the right atrium to reduce central venous pressure (CVP). Treatment for CVP was effective, as compared with two groups of 5 calves each not treated in this way, and it is assumed to be an important factor for prolongation of survival. Mineralization of driving diaphragms was present in all these calves. No preventive measures of this pathologic change were performed in this group. Another complication is hemolysis, which is partly caused by immune mechanisms initiated by administration of alpha-methyl dopa and partly by mechanical destruction due to a heavily mineralized driving diaphragm. The prevention of mineralization is another important problem for future research. Other problems, concerning the survival of TAH recipients are discussed.
Changes in serum proteins, enzymes and isoenzymes of lactate dehydrogenase (LDH) were compared in long-term surviving calves with a total artificial heart without influencing their central venous pressure (CVP) and calves in which CVP was lowered by antihypertensive drugs administered from day 60 to the end of the experiment. Antihypertensive drugs helped keep CVP within physiological levels for longer and aided liver function as well as evidenced by the different values for the parameters studied in the two groups.
A 150‐day experiment in a calf with an implanted total artificial heart, TNS‐BRNO‐II, is described. The Czechoslovak TAH‐BRNO‐II device is a hybrid; the outer housing is made of polymethylmethacrylate, the moving parts of segmented polyurethane. The blood flow through the device after the surgery gradually increased from 7 L/min to 12 L/min by the end of the experiment. Atrial pressures were automatically maintained at the same level, about one kPa on both sides. The left systolic time was automatically derived from the pump emptying phase; the right systolic time was maintained between 40% and 50%. After the surgery, normal values of blood gases, stabilization of respiratory activity, and normalization of gastrointestinal functions were reached very soon. Anticoagulant therapy was performed during the whole experiment, with several periods of increased bleeding tendency. The clinical state of the calf was essentially physiological until the 94th day of the experiment, when acute bronchopneumonia, with a high fever, over 41°C, initiated a series of complications (pseudomembranous enterocolitis, followed by sepsis lenta). The fatal complication was sudden impairment of the coagulation mechanisms on the 149th to 150th day of the experiment. This was the basic reason for the subsequent death of the animal, caused by acute cerebral anemic anoxia, which could not be prevented by immediate therapeutic procedures. In spite of these complications, the clinical state of this calf was relatively good until the end of the experiment. Autopsy revealed minimal thromboembolization at the valves. The outer surface of the diaphragm was covered with pseudoneointimal deposits and the inlet orifices were free of pannus or other connective tissue crescents. Macroscopic signs of infection were not seen, but bacteriological cultivation from internal organs confirmed Klebsiella infection. The state of the device at the time of autopsy, with simultaneous undisturbed function of the control and driving unit, showed the possibility of still longer survival.
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