Transient Vascular Occlusion Research Articles

Targeted disruption of the bcl-2 gene in mice exacerbates focal ischemic brain injury.

Neuronal death after brain ischemia is mainly due to necrosis but there is also evidence for involvement of apoptosis. To test the importance of apoptosis, we investigated the effect of targeted disruption of the apoptosis-suppressive gene bcl-2 on the severity of ischemic brain injury. Transient focal ischemia for 1 hour was induced by occlusion of the middle cerebral artery in homozygous (n=7) and heterozygous (n=6) bcl-2 knockout mice as well as in their wildtype littermates (n=5). Bcl-2 ablation did not influence cerebral blood flow but it significantly increased infarct size and neurological deficit score at 1 day after reperfusion in a gene-dose dependent manner. The exacerbation of tissue damage in the absence of Bcl-2 underscores the importance of apoptotic pathways for the manifestation of ischemic injury after transient vascular occlusion.

Spinal cord blood flow and pathophysiological changes after transient spinal cord ischemia in cats.

The goal was to study the hemodynamics and regional pathophysiological changes in the spinal cord after transient vascular occlusion in cats. We measured spinal cord blood flow (SCBF) continuously in the lumbar region with a laser-doppler flowmeter, before, during, and after spinal cord ischemia induced by balloon occlusion of the thoracic aorta, in 24 cats (divided into three groups) and simultaneously recorded the evoked spinal cord potentials (ESPs). In each group (n = 8), 10-, 20-, and 30-minute ischemic loading was performed. All animals were evaluated neurologically 36 hours later, and then their spinal cords were examined histologically. The amplitude of ESPs decreased 10 minutes and disappeared 20 minutes after occlusion. SCBF increased to as much as 2 times the control values after reperfusion and decreased gradually in all groups. Then, in all animals in the 10-minute group and six animals in the 20-minute group, SCBF returned to the control values, which were subsequently maintained throughout the experiment, and ESPs returned to normal patterns within 1 hour. For all animals in the 30-minute group and two in the 20-minute group, hypoperfusion after recirculation, irreversible amplitude changes in ESPs, postischemic paraparesis, and pathological ischemic changes in the lower thoracic and lumbar spinal segments were recognized. Our results showed that > 20-minute occlusion of the thoracic aorta in cats resulted in irreversible spinal perfusion disorders and that the monitoring of SCBF and ESPs could be useful for predicting potential neurological deficits. Furthermore, postischemic hypoperfusion may have an important role in the development of secondary spinal cord ischemia, resulting in severe neurological dysfunction. This observation suggested the possibility of therapeutic modification of the secondary processes inducing hypoperfusion after spinal ischemia.

Role of endothelium-derived relaxing factor in reactive hyperemia in canine diaphragm.

We studied the effect of NG-nitro-L-arginine (L-NA) on reactive hyperemia in the vascularly isolated hemidiaphragm of anesthetized dogs pretreated with indomethacin. In nine animals, the diaphragm was autoperfused from the left femoral artery. Phrenic arterial flow was interrupted for 10-120 s during a control period and after 20 min of L-NA infusion (6 x 10(-4) M). Postocclusive flow and duration of hyperemia during the control period increased progressively with increasing occlusion duration. After L-NA infusion, baseline and postocclusive flow in response to all occlusions declined significantly compared with control values. However, when normalized as percentage of baseline flow, postocclusive flow remained similar to that during the control period. By comparison, the duration of reactive hyperemia was significantly shortened by L-NA infusion. In five animals, we repeated the same protocol during pump perfusion of the diaphragm at a fixed flow rate. L-NA infusion increased baseline and postocclusive phrenic resistance in response to all occlusion durations; however, postocclusive phrenic resistance as percentage of baseline remained similar to control values. In addition, hyperemia durations in response to 60- and 120-s occlusions were shortened significantly by L-NA infusion. We conclude that 1) endothelium-derived relaxing factor plays an important role in the regulation of baseline vasomotor tone in the diaphragm and 2) modulation of endothelium-derived relaxing factor release contributes to the reactive vasodilatory response to transient vascular occlusion in the diaphragm.

The effect of temporary hepatic artery or portal vein occlusion in obstructive jaundice

Hepatic hemodynamics before vascular occlusion and the effect of transient hepatic artery or portal vein occlusion on the liver were investigated in normal dogs and dogs with experimentally induced obstructive jaundice by measurement of hepatic tissue blood flow (HTBF), index of hemoglobin concentration (IHb), oxygen saturation (ISO 2), serum glutamic pyruvic transaminase (SGPT) concentration, and malonedialdehyde (MDA) concentration in liver tissue. Livers with obstructive jaundice had increased blood flow and a lower hemoglobin concentration compared with normal livers at baseline before vascular occlusion. Percentage change of ISO 2 from baseline was higher than percentage change of HTBF after reperfusion in both normal and obstructive jaundiced liver, although they were decreased to almost similar proportions during vascular occlusion. MDA concentration in obstructive jaundice after reperfusion following vascular occlusion was higher than in normal liver. Furthermore, MDA concentration after reperfusion following hepatic artery occlusion was increased compared with after reperfusion following portal venous occlusion in obstructive jaundice. There was no evidence of massive liver necrosis which was newly developed by transient vascular occlusion. These results represent the pathological condition in the liver before transient vascular occlusion and after reperfusion in obstructive jaundice.

The Role of Calcium Antagonists in the Management of Renal Warm Ischemia

Eighty dogs with solitary kidneys were used to investigate the effects of calcium antagonists on the functional capacity and structural integrity of kidneys subjected to sixty minutes of warm ischemia by transient vascular occlusion under general anesthesia. Treated dogs were compared with control animals who had normal or untreated ischemic kidneys (group 1 and 2) and also with saline-flushed ischemic kidneys without or with heparinization (group 3 and 4).Verapamil and nicardipine were used independently as local (group 5 and 7) or systemic treatment (group 6 and 8).Functional and structural studies revealed that calcium antagonists improved animal survival, renal hemodynamics, renal functional capacity, cellular adenine nucleotides, and reduced the ischemic structural damage. Local treatment of ischemic kidneys with 0.15mg. nicardipine afforded the best protection against the deleterious effects of renal warm ischemia.

FRACTIONAL NECROSIS OF THE FEMORAL HEAD EPIPHYSIS AFTER TRANSIENT INCREASE IN JOINT PRESSURE. AN EXPERIMENTAL STUDY IN JUVENILE RABBITS

Ischaemia resulting from increased joint pressure may play a role in the pathogenesis of necrosis of the femoral head epiphysis. We studied the effect of temporary vascular occlusion on this epiphysis in young rabbits. Occlusion for six hours resulted in necrosis of trabecular bone and of intertrabecular marrow and vascular tissue, later followed by revascularisation and repair, as has been demonstrated previously. In contrast, raised intra-articular pressure lasting for only two hours resulted in a more complex picture: trabecular osteocytes were dead, whereas the bone-forming marrow was shown by fluorochrome labelling to remain viable, and to form appositional repair bone throughout the epiphysis. We concluded that transient vascular occlusion may cause the death of trabeculae despite intact perfusion of the bone. This type of change may be important in the pathogenesis of Perthes' disease.

Fractional necrosis of the femoral head epiphysis after transient increase in joint pressure. An experimental study in juvenile rabbits.

Ischaemia resulting from increased joint pressure may play a role in the pathogenesis of necrosis of the femoral head epiphysis. We studied the effect of temporary vascular occlusion on this epiphysis in young rabbits. Occlusion for six hours resulted in necrosis of trabecular bone and of intertrabecular marrow and vascular tissue, later followed by revascularisation and repair, as has been demonstrated previously. In contrast, raised intra-articular pressure lasting for only two hours resulted in a more complex picture: trabecular osteocytes were dead, whereas the bone-forming marrow was shown by fluorochrome labelling to remain viable, and to form appositional repair bone throughout the epiphysis. We concluded that transient vascular occlusion may cause the death of trabeculae despite intact perfusion of the bone. This type of change may be important in the pathogenesis of Perthes' disease.

Acute Reversible Pulmonary Ischemia

A 6-year-old girl with sickle cell disease was admitted to the hospital with the diagnosis of the acute chest syndrome. The laboratory findings and the radionuclear lung scan supported a diagnosis of pulmonary infarction rather than pneumonia. She improved with intravenous fluids, oxygen, penicillin, and theophylline. The most likely explanation for the rapid resolution of the clinical syndrome, the chest x-ray, and lung scan abnormalities is that masses of sickled cells caused transient pulmonary vascular occlusion leading to perfusion defects and ischemia, and that the sickled cell thrombi were dislodged before the infarction occurred. To our knowledge, this phenomenon has not been described as a cause of the acute chest syndrome in sickle cell disease in children.