Mesenchymal stem cells genetically modified with the angiopoietin-1 gene enhanced arteriogenesis in a porcine model of chronic myocardial ischaemia.

The direct injection by thoracoscope of mesenchymal stem cells (MSCs) that had been genetically modified to express angiopoietin-1 was investigated in a porcine model to determine their effect on arteriogenesis and the effectiveness of this technique. Chronic myocardial ischaemia was established using a thoracoscope to insert an ameroid constrictor around the left circumflex coronary artery. Six weeks after establishing the ischaemia, 20 pigs were randomly divided into three groups to receive injections by thoracoscope of either genetically-modified MSCs, unmodified MSCs or phosphate-buffered saline into the ischaemic border area. The injections were repeated 1 month later. The genetically modified MSCs were found to restore blood flow significantly more than the other observed treatments and immunohistochemical evaluation of arteriogenesis supported this finding. In conclusion, the injection of MSCs that had been genetically modified to express angiopoietin-1 improved arteriogenesis and increased collateral blood flow in the myocardial ischaemic area. Thoracoscope delivery of the injection was safe and minimally invasive.

Cardiac apoptosis in burned rats with delayed fluid resuscitation.

Clinical and experimental studies have shown that delayed fluid resuscitation postburn decreases heart function. We hypothesized that apoptosis occurs in the cardiomyocyte in this condition. To investigate this hypothesis, rats were burned, fluid resuscitation was delayed, and the integrity of cardiac genomic DNA in the burned rats was determined with an LM-PCR Ladder Assay kit. DNA fragmentation shown as DNA ladders on gels, the hallmark of apoptosis, was found in the heart tissue of these rats. In the early phase of delayed fluid resuscitation, the nuclear factor kappa B (NF-kappa B) was examined using an electrophoretic mobility shift assay and was found to be activated. In comparison with burned rats with immediate fluid resuscitation, nitric oxide levels in hearts from burned rats with delayed fluid resuscitation were significantly lower (P<0.01). These results suggest that apoptosis may be an important pathway for cardiac injury, which may result from the activation of NF-kappa B and decreased nitric oxide levels.

Platelet aggregation, platelet cAMP levels and thromboxane B2 synthesis in patients with diabetes mellitus.

Platelet aggregation, platelet cAMP levels and thromboxane B2 (TXB2) synthesis had been investigated in 40 diabetics (20 with microangiopathy and 20 without) and 24 normal controls. The washed platelets, but not platelet rich plasma (PRP), from the diabetics show greater sensitivity to aggregation in response to thrombin, collagen and arachidonic acid than controls (P less than 0.05). Platelets from the diabetics contain the significantly decreased cAMP levels (P less than 0.01) and synthesize the significantly greater amount of TXB2 (P less than 0.01) when induced by thrombin or collagen. Conversion of exogenously added arachidonic acid to TXB2 remained unchanged (P greater than 0.05). cAMP levels in platelets from the diabetics exhibited a significant negative linear correlation with thrombin- and collagen-induced TXB2 synthesis. There was no significant difference in platelet aggregation, platelet cAMP levels and platelet TXB2 synthesis between the diabetics with and without microangiopathy. It was suggested that in the diabetic platelets: The observed increase in platelet thromboxane A2 (TXA2) synthesis should be due to the increased activity of arachidonic acid-metabolizing system, most likely at phospholipase site; the elevated platelet TXA2 levels should inhibit platelet membrane-associated adenylate cyclase which lowered the cAMP levels in platelets; and this alternation should be the mechanism of platelet hyperaggregability, which might contribute in some way to diabetic microangiopathy.

[Effects of microiontophoretically applied flurazepam on the respiratory units in the region of the nucleus parabrachialis of the rabbit].

Experiments were carried out on 36 urethane-chloralose aneasthesized, paralyzed, vagotomized and artificially ventilated rabbits. Five-barrel glass micropipettes were used to record unit discharges and to apply flurazepam iontophoretically in the region of the nucleus parabrachialis. Inspiratory units (IUs), expiratory units (EUs), phase-spanning units (I-EUs and E-IUs) and non-respiratory units (NRUs) were observed. 26 (55.3%) out of 47 IUs, 17 (94.4%) out of 18 EUs, 11 (91.7%) out of 12 I-EUs, 2 (18.1%) out of 11 E-IUs and 43 (60.6%) out of 71 NRUs were depressed by flurazepam. The depressant ratio of EUs and I-EUs was statistically different from that of IUs and E-IUs respectively. In flurazepam sensitive 5 IUs and 2 EUs, the depressant effect could not be antagonized by GABA-A receptor antagonist bicuculline. In 10 flurazepam sensitive NRUs, there were 6 (60%) units whose depressant effect of flurazepam could be antagonized by bicuculline. In addition, the effects of acetylcholine (ACh) on the respiratory units and NRUs were examined, 15 (75%) out of 20 IUs were excited and the remaining units were not influenced. The effects of ACh on the EUs, I-EUs and E-IUs were variable, but the effects of ACh on the NRUs were mainly excitatory. In 5 IUs and 1 phase-spanning respiratory units, the depressant effect of flurazepam could not be antagonized by ACh. The results showed that flurazepam mainly depressed the EUs and I-EUs in the region of nucleus parabrachialis, thus interfering with the normal phase transition between the inspiratory and expiratory phase and reducing the respiratory rate.(ABSTRACT TRUNCATED AT 250 WORDS)