Chronic hypoxia increases fetoplacental vascular resistance in rat placenta perfused with blood.

BACKGROUND: Chronic hypoxia elevates vascular resistance on the fetal side of the placenta. However, when a low-viscosity perfusate is used, the increase in resistance caused by chronic hypoxia is relatively small (12 mmHg). In the present study, we tested the hypothesis that perfusion with more viscous fluid (blood) will reveal more substantial effect of chronic hypoxia. METHODS: Using an isolated, dually perfused rat placenta perfused at a constant flow rate with homologous blood, perfusion pressure on the fetal side was measured. Then, the relationship between perfusion pressure and flow (P/Q) was determined. RESULTS: Fetoplacental vascular resistance was increased by chronic hypoxia (10 % O2) during the last third of gestation. This was observed when the placentas were perfused with a low viscosity Krebs solution and more enhanced when perfused with blood. Nevertheless, we found no clear advantage for using blood instead of Krebs solution to study the effects of hypoxia on the fetoplacental vasculature. The elevation of fetoplacental vascular resistance caused by chronic hypoxia was at least partly resistant to acute reoxygenation. CONCLUSION: Using blood for the perfusion of the isolated rat placenta does not confer any clear methodological advantage over using Krebs solution (Tab. 2, Fig. 2, Ref. 21).

Scintigraphic detection of experimental myocardial infarction with 99mTc-heparin in the dog.

Experimental infarctions were produced in 12 dogs by ligation of the Ramus interventricularis anterior of the left coronary artery, and their uptake of 99mTc-heparin was measured 7, 24 and 48 h as well as 7 days thereafter by recording an in vivo chest scintigram 4 h after intravenous injection of the compound. The dogs were subsequently killed, the heart removed and an in vitro scintigram obtained. Finally, the uptake of the compound was measured in tissue samples. The results indicate that 99mTc-heparin is accumulated in lesions which are not older than 24 h. At the other points in time uptake is low but even 24-h old lesions cannot be demonstrated reliably. The results are impaired by the high blood activity on the cardiac chambers and by the background activity of the lungs. In general, 99mTc-heparin has less useful properties than the more frequently employed 99mTc-pyrophosphate so that a change of procedure is not to be recommended.

Pyrophosphate scintigraphy and other non-invasive methods in the detection of cardiac involvement in some systemic connective tissue diseases.

Thirteen patients with systemic lupus erythematosus, 8 patients with polymyositis, and 6 patients with spondylitis ankylopoetica (Bechterew's disease) underwent clinical cardiologic examination and scintigraphy of the myocardium (99mTc-pyrophosphate), ECG, echocardiography, polygraphy, and their blood pressure was taken. The aim of the study was to ascertain how such a combination of non-invasive examinations can help in recognizing a cardiac involvement. In systemic lupus erythematosus cases one or more positive findings were revealed in 9 patients (69%), in 4 patients all examinations were negative (31%). Four patients (50%) with polymyositis had positive findings. In patients with spondylitis ankylopoetica positive findings occurred in 2 cases (33%). The study has shown that a combination of non-invasive cardiologic methods increases the probability of detecting cardiac involvement in systemic connective tissue diseases.

99mTc-aminohexylidendiphosphonate and 99mTc-pyrophosphate in the scintigraphic diagnosis of experimental cardiomyopathy in dogs.

Experimental cardiomyopathy was provoked in 24 dogs with high intravenous doses of adrenaline and theophylline. These lesions were studied by means of the new agent 99mTc-AHDP and 99mTc-PYP in comparison. Cardiomyopathy could be imaged as early as 4 h after the onset of involvement but not later than 7 days. A maximum accumulation occurred in lesions 24 h old. 99mTc uptake in the myocardium was graded scintigraphically. 99mTc-AHDP was accumulated in the altered myocardium to a greater extent than 99mTc-PYP. Scintigraphic findings were in good agreement with plasma levels of creatine-kinase. A comparison with histology demonstrated that the maximum accumulation of radiopharmaceuticals occurred at the time when the development of myocardium involvement reached the stage of myocytolysis.

Scintigraphic myocardial imaging with 99mTC-labelled pyrophosphate of experimentally produced cardiomyopathy in dogs.

Scintigraphic examination of the myocardium using 99mTc-labelled pyrophosphate was carried out in 10 dogs with experimentally produced cardiomyopathy. This was brought about by intravenous administration of high doses of adrenalin and theophylline. The scan was positive in 8 out of 10 dogs. "Hot" foci were very extensive. The degree of accumulation was however low (2+). Histological examination of the myocardium using the light microscope showed only scarcely distinguishable damage to the tissue without the presence of necrosis. ECG examinations were normal in all cases. By means of 99mTc-labelled pyrophosphate even very small myocardial disorders can thus be detected. This fact may be of clinical importance for an early diagnosis of heart lesions.

Pyrophosphate scan of the temporarily ischemized dog myocardium.

In 9 dogs a transient myocardial ischemia was provoked using complete occlusion of the ramus interventricularis anterior of the left coronary artery. The occlusion was removed after 5, 10 or 15 min. Four hrs after removal of the occlusion a scan of the myocardium was carried out using 99mTc-labelled pyrophosphate. In 7 out of 9 dogs under study the scan was markedly positive, in 2 dogs negative. ECG demonstrated ischemic changes practically in all dogs; the changes became normal after removal of the occlusion, namely in 5 to 35 min. The histological examination of the tissue demonstrated in all 9 dogs only a slight impairment of the myocardium.

[Scintigraphic diagnosis of experimentally induced pericarditis in dogs using 99mTc-labelled pyrophosphate (author's transl)]. / Szintigraphische Diagnostik der experimentellen Perikarditis des Hundes mittels 99mTc-Pyrophosphat.

In the present paper the possibilities of scintigraphic diagnosis of experimental pericarditis are discussed. Pericarditis was induced by either talc or formaldehyde intrapericardially. In all animals the administration of talc as well as formaldehyde produced inflammatory changes which were more serious after formaldehyde. The scan of the talc pericarditis was carried out on the 7th day after operation and of the formaldehyde pericarditis on the 3rd, 7th or 14th days. No positive scintigraphic finding was made in any of the experimental animals, apart from a massive incorporation in the operation scars. The counting of radioactive impulses after the exstirpation of the tissue samples confirmed the scintigraphic findings. Statistical evaluation did not reveal any essential difference between the accumulation of the radiopharmaceutical into the pericarditis as well as into the pericardial bag in comparison with the control animals. Although our model does not exactly reflect the situation of patients suffering from pericarditis it may be assumed that pyrophosphate scintigraphy is not suitable for the diagnosis of acute pericarditis in clinical practice.

Scintigraphic myocardial imaging with 99mTc-labelled gluconate of experimentally produced cardiomyopathy in dogs.

In 10 dogs experimental cardiomyopathy was produced using high intravenous doses of adrenaline and theophylline. The possibility of scintigraphic detection of this non-ischaemic damage was tested by means of 99mTc-gluconate. In 5 dogs the scintigraphic examination was carried out 4 hrs following the production of the damage. In all 5 cases a marked positivity of the heart scan was observed. The finding was confirmed by the radioactivity of tissue samples from all sections of the heart. In 3 out of 5 dogs the histological examination of the myocardium (PAS and HBFP staining) was positive. In the remaining 5 dogs the scan was performed 24 hrs following the development of the damage. A positive scintigraphic finding was observed in 4 cases, the degree of accumulation being lower than at 4 hrs. The radioactivities of tissue samples were also significantly lower as compared with the 4-hr values. In contrast, the histological findings were markedly positive in all 5 dogs. It follows that 99mTc-gluconate is capable of detecting in addition to infarctions non-ischaemic damages to the myocardium, too. The normalization of the finding is very quick. This experimental finding appears to be of importance in clinical practice.

Scintigraphic detection of experimental myocardial infarction with 99mTc-2,3-dimercaptosuccinic acid.

Acute myocardial infarctions were produced by ligature of the left frontal descending coronary artery in 9 dogs. The possibility of scintigraphic imaging with 99mTc-DMSA 4 hrs after intravenous administration was studied. The infarctions were 4, 24 and 48 hrs old. The in vivo scan was positive in only one dog with a 4-hr old infarction. The in vivo scans were confirmed by the analysis of the radioactivity in tissue samples. The accumulation of the radiopharmaceutical increased slightly in 48-hr old lesions; however, this increase was not sufficient for a positive scintigraphic finding. Thus, we do not recommend 99mTc-DMSA for clinical use in acute lesions.

The pyrophosphate heart scintigram in children with progressive muscular dystrophy.

A pyrophosphate heart scintigram was obtained in 16 boys with progressive muscular dystrophy Duchenne. All of them showed pathological ECG findings and high plasma levels of CK, AST, ALT and LD. In 4 patients the scintigram was distinctly positive and in further 3 it reached borderline values. The remaining 9 boys had normal scintigraphic findings. Those with a positive heart scintigram had very high plasma levels of the enzymes under study which was suggestive of current progression of the disease. There was, however, no relation between heart scintigraphy and the affliction of the skeletal muscles expressed by means of an index.

99mTc-aminohexylidendiphosphonate and 99mTc-pyrophosphate in the scintigraphic diagnosis of experimental myocardial infarction in dogs.

99mTc-aminohexylidendiphosphonate (99mTc-AHDP) is a new Czechoslovak pharmaceutical of the phosphonate line which contains the amino group NH2 in its molecule. This substance was tested in 5 dogs with experimentally provoked 48-h old myocardial infarction. The in-vivo scan and the radioactivity of tissue samples demonstrated that 99mTc-AHDP is as suitable for imaging acute myocardial infarction as is the commonly used 99mTc-pyrophosphate.

Rho-kinase inhibition attenuates acute hypoxic fetoplacental vasoconstriction in the rat.

The vessels on the fetal side of the placenta differ from most other vascular beds except the lungs in that they respond to acute hypoxia by vasoconstriction. An essential role of calcium influx in the mechanism of this hypoxic fetoplacental vasoconstriction (HFPV) has been shown previously. That finding does not, however, exclude the possible involvement of other mechanisms of vascular tone regulation. In this study we tested the hypothesis that Rho-kinase-mediated calcium sensitization is involved in HFPV. We used a model of isolated rat placenta dually perfused (from both the maternal and fetal side) with Krebs salt solution saturated with normoxic and hypoxic gas mixture respectively at constant flow rate. Rho-kinase pathway was inhibited by fasudil (10 microM). We found that fasudil reduced basal normoxic fetoplacental vascular resistance and completely prevented HFPV. This suggests that the activity of Rho-kinase signaling pathway is essential for HFPV.