Different phenotype manifestation of familial adenomatous polyposis in families with APC mutation at codon 1309.

Germline mutation in APC gene induced development of familial adenomatous polyposis (FAP). The risk of developing specific manifestation of FAP is often correlated with the position of the inherited APC mutation. Patients with mutations localized in the largest exon 15 between codons 1286 and 1513 (mutation cluster region, MCR) have generally a worse prognosis with early onset of the disease. We found 6 FAP families with mutation at codon 1309 (3927_3931delAAAGA) in the cohort of 39 FAP Slovak families with rapid cancer progress. In addition, mutation in codon 1309 was detected in three family members, one of them with a very different phenotype. This oldest family member, aged 81, has persisted asymptomatic without clinical manifestations.

[Right-sided mechanical circulatory support in acute right ventricular failure in the dog]. / Pravostranný mechanický podporný obeh pri akútnom zlyhaní pravej komory u psa.

The technique of surgically induced acute progressive right ventricular failure in experimental animals is described. It sumultates the hemodynamic situation of right ventricular failure in some patients after termination of extracorporeal circulation applied for carrying out procedures on the left ventricle. The described technique consists of rightsided longitudinal ventriculotomy, destruction of the tricuspid valve, and ligation of the right coronary artery. Nine control dogs died within two hours after induction of failure due to low stroke volume caused by low pulmonary and left atrial pressure. The use of rightsided support appliance draining blood from the right atrium in systole and pumping it into the trunk of the pulmonary artery in diastole by means of a membrane pump resulted in further 12 dogs in the restoration of left ventricular diastolic pressure, significant increase of aortal pressure (p less than 0.003) and stroke volume (p less than 0.003) and in a decrease of right atrial pressure (p less than 0.003). The study demonstrated that by using the described mechanical support the circulation can be adequately assisted so that the failing right side of the heart can get restored. (Tab.1,Fig.5,Ref.25.).

Haemodynamics in the first seconds after coronary artery occlusion.

The changes in cardiac and in total haemodynamics, occurring during the first seconds of occlusion and the subsequent desocclusion of coronary arteries were studied on 28 dogs. The most intensive changes were observed after the trunk occlusion of the left coronary artery. Simultaneously with decreasing blood inflow into the myocardium its contractility and the systolic pressure in the left ventricle and the outflow from the coronary sinus began to fall rapidly. The systolic pressure in the left ventricle decreased within the first 10 s from 24 to 13-15 kPa (180 to 100-110 mm Hg), which means that the systolic pressure fell about 1 kPa (7-8 mm Hg) per second, or 0.5-0.6 kPa (4-5 mm Hg) per systole. At the same time the end-diastolic pressure in the left ventricle also increased from zero to 3-4 kPa (25-30 mm Hg). After the trunk desocclusion of the left coronary artery the systolic pressure in the left ventricle proceeded to fall by about 2-3 kPa (15-22 mm Hg). Only then, 20-25 s after the desocclusion, blood flow in the left coronary artery began to rise intensively and 4-6 s later the myocardial contractility and the systolic pressure in the left ventricle also increased. After unclamping (50-60 s), there was an overshoot of haemodynamic values above preocclusive values and then followed the compensatory phase. This phase lasted 80-90 s and on its peak the pressure and flow parameters increased by about 50-60% above preocclusive values. During the occlusion of ramus interventricularis anterior or ramus circumflexus for 30-60 s the haemodynamic parameters changed only slightly. The same was observed during trunk occlusion of the right coronary artery (30-60 s), but in that case many extrasystoles occurred.

[The most frequently used methods of assisted circulation]. / Nejpouzivanejsie metódy asistovanej cirkulácie.

An account of the most widely used mechanical synchronized types of assisted circulation for the control and management of circulatory failure. Intraaortal ballon counterpulsation is in specialized departments already a routine method. When comparing intraaortal ballon counterpulsation with the bypass method of volume relief of the ventricle, based on the bioenergetic index, the latter method of assisted circulation is more effective. The authors draw attention to the bypass method of assisted circulation involving transdiaphragmatic cannulation of the left ventricle--aorta by laparotomy, without thoracotomy.

[The effect of diltiazem (Lachema) on transmural non-homogeneity of histochemical changes due to the Ca-paradox]. / Transmurálna nehomogénnost' histochemických zmien po Ca-paradoxe a po jeho ovplyvnení diltiazemom (Lachema).

Calcium paradox was induced by 2.5 min perfusion of the rat heart (Langedorf's system) at 37 degrees C with calcium-free Krebs--Henseleit solution and subsequent 10 min reperfusion with the same solution containing calcium. Ca2+ depletion itself did not affect the activities of the histochemically studied enzymes (succinate dehydrogenase, lactate dehydrogenase, beta-hydroxybutyric dehydrogenase, phosphorylase, and ATPases). Ca paradox was histochemically characterized by decrease and even disappearance of activities of the given enzymes and by marked transmural nonhomogeneity of these changes exhibiting a decreasing trend towards the endocardium. Diltiazem in the concentration of 0.4 and particularly of 4.0 mumol.l-1 exerted a protective effect manifested by a better preservation of the enzymatic activities.

[Assisted circulation for volume relief of the right heart ventricle]. / Die assistierte Zirkulation zur Volumenentlastung der rechten Herzkammer.

The model of the failure of the right ventricle was formed in dog experiments. The animals were connected with the right mechanically assisted circulation. The blood was pumped synchronously with the heart action from the right atrium directly to the pulmonary artery by temporary bypass of the right ventricle. The right volume relief improved (p less than 0.03) the decisive hemodynamic parameters. The value of assisted circulation in case of the hitherto only difficulty to controlled failure of the right ventricle is proved with that.

Diminution of "reperfusion injury" in reperfused ischemic myocardium by phenothiazines. A quantitative morphological study.

The effect of pretreatment by phenothiazines--Chlorpromazine (CPR) /Spofa/ and Trifluoperazine (TFP) /Smith Kline and French/ on reperfusion injury of ischemic myocardium were studied. Reperfusion of ischemic myocardium following an ischemic period exceeding 40 min resulted in morphological, physiological and biochemical changes identical with those induced by enhanced cytosolic Ca2+ concentration. Left descending coronary ligation was performed on 70 dogs divided into four group. Group I: permanent occlusion (5 dogs--60 min, 5 dogs--120 min, 5 dogs--180 min); group II: 15 dogs (60 min occlusion + 120 min reperfusion); group III: 20 dogs (60 min occlusion, 15 mg CPR, reperfusion 120 min); group IV: 20 dogs (60 min occlusion, 2 mg TFP + 120 min reperfusion). CPR or TFP were administered 30 min after the ligation. The effect of drugs was quantified on tetrazolium stained gross sections and studied from physiological, biochemical and ultrastructural points of view. Treatment of animals with phenothiazines, known as calmodulin inhibitors, considerably improved the ultrastructure of myocytes in area at risk, and allowed for the recovery of at least 60 per cent of injured myocytes after reflow restoration. Ultrastructural findings tightly correlate with physiological and biochemical results.

Diminution of injury in reperfused ischemic myocardium by phenothiazines. A quantitative morphological study.

Left descending coronary ligation was performed on 70 dogs and divided into four groups. I. group - permanent occlusion (5 dogs 60 min, 5 dogs 120 min, 5 dogs 180 min), II. group - 15 dogs (60 min occlusion + 120 min reperfusion), III. group - 20 dogs (60 min occlusion, 15 mg Chlorpromazine [CPR], reperfusion 120 min), IV. group - 20 dogs (60 min occlusion, 2 mg Trifluoperazine [TFP] + 120 min reperfusion). CPR or TFP were administered 30 min after the ligation. Effect of drugs was quantified on tetrazolium stained gross sections and studied from physiological, biochemical and ultrastructural points of view. Results reveal that treatment of animals with phenothiazines revealing calmodulin inhibitory action, considerably improved the ultrastructure of myocytes in area at risk and allowed for recovery at least 60 per cent of injured myocytes after restoration of reflow. Ultrastructural findings tightly correlate with physiological and biochemical results.