Effect of Transmural Pressure on Constrictor Reactions of Caudal Artery in Hypotensive and Hypertensive Rats

Clipping of the abdominal aorta distally to the renal arteries produces a persistent decrease in blood pressure in hindquarter vessels by 35-40%. On week 6-7 postoperation, the reactions of the caudal artery perfused in vitro under constant pressure to norepinephrine were studied. At transmural pressure of 150 mm Hg, the vascular responses in hypotensive rats were reduced compared to those in normotensive control. By contrast, the responses of hypertensive vessels were more pronounced at 75 mm Hg even after deendothelization.     

Absence of the left inferior thyroid artery: clinical implications

Dissection of an adult male cadaver revealed an absence of the left inferior thyroid artery; its usual area of distribution to the thyroid gland was supplied by the right inferior thyroid artery. Absence of the left inferior thyroid artery occurs in 1-6% of cases. The inferior thyroid artery arises commonly from the thyrocervical trunk, passes posterior to the carotid sheath and supplies the inferior pole of the corresponding lobe of the thyroid gland; its branches can course anterior or posterior to or between branches of the recurrent laryngeal nerve. During thyroid surgery it is imperative to identify the relationship of the inferior thyroid artery to the recurrent laryngeal nerve or to establish its absence because injury to the nerve can be a major complication; awareness of significant variations of the surgical anatomy of the thyroid gland is vital for preserving the integrity of important structures.     

A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease: relationships with C677T polymorphism and homocysteine/folate metabolism

5, 10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in homocysteine/methionine metabolism. The most-studied C677T polymorphism in the MTHFR gene results in a thermolabile variant with reduced activity, and is associated with increased levels of total plasma homocysteine, a risk factor for coronary artery disease. A new mutation in the MTHFR gene (A1298C) has also been reported to lower enzyme activity. Whether A1298C is a risk factor for coronary artery disease, separately or in combination with C677T, and/or relative to total plasma homocysteine and folate status, is unclear to date. We evaluated this hypothesis in 470 angiographically characterized subjects, 302 with coronary artery disease, and 168 with normal coronary arteries. The frequency of the 1298C allele was 0.33 and that of combined heterozygosity 0.315. No difference was found in the frequency of the genotypes or when analyzed for combined heterozygosity between patients with coronary artery disease and normals. Independent of folate status, the 1298C allele was not associated with increased total plasma homocysteine. No additional effect of A1298C on total plasma homocysteine was observed in 148 combined heterozygotes compared with 98 heterozygotes for the C677T alone. These findings do not support a major role for the A1298C mutation in homocysteine metabolism and emphasize the hypothesis that MTHFR genotypes may interfere with coronary artery disease risk only when an unbalanced nutritional status leads to raised total plasma homocysteine levels.     

Separating the direct effect of hypoxia from the indirect effect of changes in cardiac output on the maximum pressure difference across the tricuspid valve in healthy humans

In healthy humans, changes in cardiac output are commonly accommodated with minimal change in pulmonary artery pressure. Conversely, exposure to hypoxia is associated with substantial increases in pulmonary artery pressure. In this study we used non-invasive measurement of an index of pulmonary artery pressure, the maximum systolic pressure difference across the tricuspid valve (P_max), to examine the pulmonary vascular response to changes in blood flow during both air breathing and hypoxia. We used Doppler echocardiography in 33 resting healthy humans breathing air over 6–24 h to measure spontaneous diurnal variations in P_max and cardiac output. Cardiac output varied by up to ~2.5 l/min; P_max varied little with cardiac output [0.61±0.74 (SD) mmHg min l^–1]. Eight of the volunteers were also exposed to eucapnic hypoxia (end-tidal ) for 8 h. In this group P_max rose progressively from 21 mmHg to 37 mmHg over 8 h. By comparing diurnal variations in P_max during air breathing with changes in P_max during hypoxia in the same eight individuals, we concluded that only approximately 5% of the changes in P_max during hypoxia could be attributed to concurrent changes in cardiac output. The low sensitivity of P_max to changes in cardiac output makes it a useful index of hypoxic pulmonary vasoconstriction in healthy humans.     

Severe hypoxia decreases oxygen uptake relative to intensity during submaximal graded exercise

Summary The effect of severe acute hypoxia (fractional concentration of inspired oxygen equalled 0.104) was studied in nine male subjects performing an incremental exercise test. For power outputs over 125 W, all the subjects in a state of hypoxia showed a decrease in oxygen consumption ( O₂) relative to exercise intensity compared with normoxia (P < 0.05). This would suggest an increased anaerobic metabolism as an energy source during hypoxic exercise. During submaximal exercise, for a given O₂, higher blood lactate concentrations were found in hypoxia than in normoxia (P < 0.05). In consequence, the onset of blood lactate accumulation (OBLA) was shifted to a lower O₂ ( O₂ 1.77 l·min^–1 in hypoxia vs 3.10 l·min^–1 in normoxia). Lactate concentration increases relative to minute ventilation ( _E) responses were significantly higher during hypoxia than in normoxia (P < 0.05). At OBLA, _E during hypoxia was 25% lower than in the normoxic test. This study would suggest that in hypoxia subjects are able to use an increased anaerobic metabolism to maintain exercise performance.     

The response of heat shock proteins 25 and 72 to ischaemia in different kidney zones

 Induction of heat shock proteins (HSPs) following cell injury contributes to the protection of vital cell functions. It was, therefore, of interest to study the effects of transient renal ischaemia on the abundance and distribution of two HSPs, HSP25 and HSP72, in renal tissue using Western-blot techniques. Analyses were performed on the supernatant (HSP25, HSP72) and pellet (HSP25) of homogenates obtained from cortex (CX) and outer (OM) and inner (IM) medulla of the rat kidney immediately after 60 min of ischaemia followed by varying periods of reperfusion. Ischaemia of the left kidney caused HSP25 contents to decrease in CX, OM and IM by 73, 89 and 54% respectively, compared with the corresponding zones of the contralateral control kidney. This initial decrease in supernatant HSP25 was accompanied by an increased abundance of HSP25 in the pellet. Following reperfusion, HSP25 contents in the supernatant gradually increased in CX and OM, reaching, after 24 h, values that were 5.4- and 2.5-fold higher, respectively, than those in the control kidneys. After 7 or 14 days of reperfusion, HSP25 contents had not completely normalised in CX, but had reached control levels in OM. In IM, the HSP25 content remained below control throughout the entire reperfusion period. HSP72 (supernatant) was below the detection limit in the CX of the control kidney. Similar to the level of HSP25, that of HSP72 was also markedly lower in OM and IM immediately after ischaemia. The intrarenal distribution of HSP72 and the sequence of zonal changes in HSP72 contents were similar to those observed for HSP25. These results are compatible with the view that, during ischaemia and the initial reperfusion period, HSP25 migrates from the cytoplasmic compartment (supernatant) into the nucleus and/or associates with cytoskeletal structures. The observation that both HSP25 and HSP72 are transiently induced in CX and OM, but not in IM, may be explained by the fact that, while all kidney cells are exposed to ischaemic stress, only inner medullary cells experience a major postischaemic attenuation of osmotic stress. Received: 11 February 1997 / Received after revision and accepted: 26 March 1997     

Ectopia lentis in Loeys‐Dietz syndrome type 4

Loeys‐Dietz syndrome is a heritable disorder of the connective tissue leading to multisystem involvement including craniofacial features, skeletal abnormalities, cutaneous findings and early‐onset and aggressive disease of the aorta and its branches. There are multiple types of Loeys‐Dietz syndrome related to pathogenic variants in TGFBR1, TGFBR2, SMAD3, TGFB2, and TGFB3. Individuals with Loeys‐Dietz syndrome may be misdiagnosed as having Marfan syndrome due to shared phenotypic features and aortic root dilation. However, ectopia lentis has been an important discriminating feature, being unique to Marfan syndrome and not reported to be associated with Loeys‐Dietz syndrome. We report the case of a 46‐year‐old woman with Loeys‐Dietz syndrome type 4 due to a pathogenic variant in TGFB2 who was diagnosed with ectopia lentis at age 44. The patient underwent whole exome sequencing and no other pathogenic variants were found to explain the ectopia lentis. Our findings indicate that ectopia lentis may be an uncommon finding in Loeys‐Dietz syndrome type 4 and emphasize the importance of genetic testing in familial thoracic aortic aneurysm disease.     

The relationship between exposure duration,carboxyhemoglobin, blood glucose,pyruvate and lactate and the severity of intoxication in 39 cases of acute carbon monoxide poisoning in man

The relationship between exposure duration, COHb, blood glucose, pyruvate and lactate and the severity of intoxication was investigated in a group of 39 cases of acute CO poisoning treated in the Clinical Toxicology Center in ód, Poland.On the basis of clinical criteria the patients were classified into cases of mild, moderate, severe and very severe CO poisoning. COHb and carbohydrate metabolites were estimated in venous blood taken immediately after admission of the patient to hospital prior to treatment.The severity of intoxication did not correlate with blood COHb; variation in exposure duration seems to be responsible for this phenomenon. Severe and very severe poisonings were associated with longer exposures and were accompanied by a markedly higher blood lactate level, compared to mild and moderate cases. Blood pyruvate depended less than lactate on the severity of intoxication. Blood glucose depended neither on exposure duration nor on the severity of intoxication.Among the carbohydrate metabolic parameters studied, blood lactate determination can be helpful in the evaluation of the severity of CO poisoning in man.     

Ketanserin causes surmountable antagonism of 5-hydroxytryptamine-induced contractions of large coronary arteries of dog

Summary Large coronary arteries of the dog were contracted with 5-hydroxytryptamine (5-HT). The 5-HT₂-receptor antagonist ketanserin antagonized the 5-HT-induced effects. Unlike Brazenor and Angus (Europ J Pharmacol 81: 569–576, 1982), who reported insurmountable antagonism of the effects of 5-HT in dog coronaries, we found that the antagonism by ketanserin can be surmounted, provided the concentrations of 5-HT are high enough. Ketanserin also unmasked a saturable component of the 5-HT-induced contractions. Although ketanserin (0.1–1 mol/l) depressed the maximal force of the saturable component, it did not change its EC₅₀ (-log mol/l 8.0). We conclude that large coronary arteries of dog are contracted by 5-HT mainly though 5-HT₂-receptors and to a smaller extent through receptors different from 5-HT₂.     

Overall results in 304 consecutive patients with acute spontaneous subarachnoid hemorrhage

The results obtained in 304 consecutive patients with spontaneous subarachnoid hemorrhage are described, the majority of whom (86%) were admitted while in acute condition. Only 46% of the patients in this series were in good condition at admission. The initial management was standardized for all patients, but the protocol of "delayed surgery" was applied to patients with subarachnoid hemorrhage from aneurysmal rupture. Two hundred and twenty-two patients (73%) had intracranial aneurysms. Of these, 20 (9%) were moribund and died shortly after admission; nine (4%) underwent emergency surgery due to the coexistence of a life-threatening cerebral hematoma; seven (3%) were operated upon within 3 days of admission; 78 (35%) died after rebleeding or after steady deterioration of the patient's condition due to vasospasm while awaiting surgery. Of the remaining 108 patients ready for delayed surgery, 12 (11%) (operation refused, elderly patients in poor general condition, spontaneous thrombosis of the aneurysm) were treated conservatively, and 96 (89%), who were in various clinical conditions, were actually operated on. Of these 96 patients, 79 (82%) exhibited excellent or good results, 5 (5%) were disabled, and 12 (12%) died. In the authors' experience, the overall management of intracranial aneurysms in unselected patients according to the protocol of delayed surgery results in significant loss of patients awaiting surgery, and good surgical results in the survivors.