A chronic mouse model of myocardial ischemia-reperfusion: essential in cytokine studies.
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Reperfusion of the ischemic myocardium is associated with a cytokine cascade that reflects a cellular response to injury. We studied this cascade in the mouse and found that acute surgical trauma in sham-operated animals obscured early changes in cytokine induction that occur during myocardial ischemia-reperfusion (MI/R). Therefore, we utilized a new implantable device that allows occlusion and reperfusion of the left anterior descending coronary artery in a closed-chest mouse at any time after instrumentation. Induction of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha mRNA in the whole heart was examined by RNase protection assay and quantitated by Phosphor- Imager. At 3 h after instrumentation, levels of IL-6 mRNA in sham-operated animals increased above those of control naive hearts, whereas this increase did not occur until after 1 day for TNF-alpha mRNA. The surgical trauma led to exaggeration of I/R cytokine induction with greater variance in response. At 3 days and 1 wk after instrumentation, levels of both IL-6 and TNF-alpha mRNA in sham-operated animals were comparable to those of naive hearts and induction responses in I/R were much less variant. We also found that 1 h of ischemia and 2 h of reperfusion at all time points of recovery (i.e., 3 h and 1, 3, and 7 days after instrumentation) led to a significant increase in IL-6 and TNF-alpha mRNA levels. In addition, 3 h of permanent occlusion, which did not induce any mRNA increase after 1 wk postinstrumentation, caused marked upregulation of IL-6 mRNA in an acutely prepared animal. This study of early cytokine responses evoked by MI/R highlights the need for dissipation of acute surgical trauma by using a chronic, closed-chest mouse preparation. (+info)
Cellular basis for contractile dysfunction in the diaphragm from a rabbit infarct model of heart failure.
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Abnormal respiratory muscle function is thought to contribute to breathlessness and exercise intolerance in heart failure but little is known about possible alterations in the function of such muscle. We have measured tetanic force and intracellular Ca(2+) concentration ([Ca(2+)](i)) in isolated, arterially perfused hemidiaphragm preparations from a rabbit coronary artery ligation model of heart failure. Increasing stimulation frequency (10-100 Hz) caused a progressive increase of force and [Ca(2+)](i) in control preparations, whereas force and [Ca(2+)](i) only increased between 10 and 25 Hz stimulation (decreasing at higher frequencies) in preparations from ligated animals. Cyclopiazonic acid produced a dose-dependent shift in the relationship between stimulation frequency and [Ca(2+)](i) in control preparations that was similar to the shift observed in the diaphragm of coronary-ligated animals. These data indicate that the in vitro contractile characteristics of the diaphragm are significantly altered in our model and that altered [Ca(2+)](i) regulation contributes to the reduced diaphragm strength observed in heart failure. (+info)
Surgical treatment of extracranial internal carotid artery aneurysms.
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PURPOSE: Extracranial internal carotid artery aneurysms (EICAs) can be treated by carotid ligation or surgical reconstruction. In the consideration of the risk of stroke after internal carotid artery (ICA) occlusion, the aim of this study was to report the results of reconstructive surgery for these aneurysms, including lesions located at the base of the skull. METHODS: From 1980 to 1997, 25 ICA reconstructions were performed for EICA: 22 male patients and 3 female patients (mean age, 54.4 years). The cause was atherosclerosis (n = nine patients), dysplasia (n = 12 patients), trauma (n = three patients), and undetermined (n = one patient). The symptoms were focal in 15 cases (12 hemispheric, three ocular), nonfocal in three cases (trouble with balance and visual blurring), and glossopharyngeal nerve compression in one case. Six cases were asymptomatic, including three cases that were diagnosed during surveillance after ICA dissection. In nine cases, the upper limit of the EICA reached the base of the skull. A combined approach with an ear, nose, and throat surgeon allowed exposure and control of the ICA. RESULTS: After operation, there were no deaths, one temporary stroke, two transient ischemic attacks, and 11 cranial nerve palsies (one with sequelae). The ICA was patent on the postoperative angiogram in all but one case. During follow-up (mean, 66 months), there were two deaths (myocardial infarction), one occurrence of focal epileptic seizure at 2 months, and one transient ischemic attack at 2 years. In December 1998, duplex scanning showed patency of the reconstructed ICA in all but one surviving patient. CONCLUSION: Surgical reconstruction is a satisfactory therapeutic choice for EICA, even when located at the base of the skull. (+info)
Alpha-adrenergic blockade in preventing posttransplant edema of lung allograft.
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Effect of alpha-adrenergic blockers on pulmonary edema in lung transplantation was studied with a rat model of syngeneic left lung transplantation. Prior to harvesting, 0.1 mg of Prazosin or 0.4 mg of Yohimbine was given to the donor. Pulmonary and systemic hemodynamics were measured under the right pulmonary arterial occlusion (RPAO) at different time points after grafting. Wet to dry weight ratio (W/D) of all transplants was also calculated. Same procedure was conducted in rats with normal and ischemic lung and in transplanted animals without any treatments. While RPAO did not increase W/D in normal lung with a significant elevation in pulmonary arterial pressure (PAP), both these values significantly increased in transplanted lung. Transplanted animals could not tolerate RPAO 24 hours after grafting, but were tolerable later than 48 hours with elevated W/D and PAP. On the contrary, animals given Prazosin or Yohimbine were all tolerable at 24 hours postsurgery. Yohimbine significantly improved W/D. Consequently, it was demonstrated that pulmonary edema of the graft reached its peak during first 24 to 48 hours after transplantation and was alleviated by the blockade of alpha-adrenergic receptor in the graft vessel. (+info)
Haemodynamic and renal evolution of the bile duct-ligated rat.
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In the present study we have characterized the evolution of changes in systemic haemodynamics (thermodilution in conscious animals) and sodium balance (metabolic cages) in a model of liver cirrhosis induced by chronic bile duct ligation (BDL). Mean arterial pressure (BDL, 111.5+/-4.7 mmHg; sham-operated, 122.9+/-3.0 mmHg) and peripheral vascular resistance (BDL, 2.63+/-0.08 units; sham-operated, 2.93+/-0.09 units) were lower in BDL rats from day 12 after surgery and decreased progressively throughout the following days. Portal hypertension was evident earlier in BDL rats and was maintained throughout the study period. Cardiac index (BDL, 58.8+/-3. 9 ml.min(-1).100 g(-1); sham-operated, 43.9+/-1.5 ml.min(-1).100 g(-1)) and stroke volume (BDL, 147.2+/-12.7 ml.beat(-1).100 g(-1); sham-operated, 109.0+/-4.2 ml.beat(-1).100 g(-1)) were significantly elevated in the BDL rats only from day 18 after surgery. There were no significant differences in sodium balance between the groups until day 16 after surgery, at which time BDL animals started to retain significantly more sodium than the controls. Sodium retention increased progressively, and at day 20 BDL rats had retained 0.7 mmol/100 g more than the control animals (accumulated retention: BDL, 2.2+/-0.2 mmol/100 g; sham-operated, 1.5+/-0.2 mmol/100 g). Plasma renin activity and aldosterone concentration were not elevated in the BDL animals at days 12, 16 or 20 after surgery. These data indicate that the BDL rat model shows early portal hypertension, peripheral vasodilation and arterial hypotension, several days before sodium retention is detectable, and in the absence of changes in plasma levels of renin and aldosterone. Overall, these data suggest that, in the BDL rat model, sodium retention is secondary to portal hypertension and peripheral vasodilation. (+info)
Long-term follow-up study of patients with cavernous sinus aneurysm treated by proximal occlusion.
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Proximal occlusion of the internal carotid artery (ICA) is still the treatment of choice for a large cavernous sinus aneurysm. Endovascular occlusion or trapping of the ICA with or without an extracranial-intracranial bypass is sometimes performed. We analyzed the results of the long-term follow up of 11 patients with a giant or large cavernous sinus aneurysm treated by only proximal occlusion between 1975 and 1989. Proximal occlusion of the carotid artery was performed by Selverstone clamping. The follow-up period ranged from 6 to 21 years (mean 13.9 years). Eight of the 11 patients showed improvement of cranial nerves paresis or headache, and four became asymptomatic. None of the original aneurysms ruptured. The final outcomes were nine good recovery, one moderately disabled, and one severely disabled by the Glasgow Outcome Scale. The causes of morbidity were early ischemia and subarachnoid hemorrhage from a newly formed aneurysm. Late complications included ischemia in two patients, and new formation and enlargement of aneurysms at a site other than the original aneurysm in two patients, 13 and 17 years later. Therapeutic carotid artery occlusion requires strict test ICA occlusion. In addition, long-term follow up by periodical cerebral angiography using magnetic resonance, computed tomography, or digital subtraction angiography is necessary, and postoperative medical treatment is important to reduce the risk of late complications. (+info)
Complications associated with intraarterial administration of papaverine for vasospasm following subarachnoid hemorrhage--two case reports.
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Complications associated with intraarterial papaverine infusion occurred in two patients treated for vasospasm due to subarachnoid hemorrhage (SAH). A 42-year-old male with an anterior communicating artery aneurysm underwent craniotomy and aneurysm clipping. Five days after the SAH occurred, angiography demonstrated moderate vasospasm in spite of hypervolemic-hypertensive therapy. During papaverine infusion into the carotid artery, he suffered loss of consciousness due to a seizure for a few minutes. A 61-year-old female with a right internal carotid-posterior communicating artery aneurysm underwent clipping. Six days after the SAH occurred, angiography demonstrated severe vasospasm in spite of hypervolemic-hypertensive therapy. Angiography performed immediately after papaverine infusion into the carotid artery revealed exacerbation of the vasospasm. Finally she suffered cerebral infarction and died. Complications of intraarterial papaverine infusion are potentially dangerous. We recommend trial administration of papaverine with angiography and neurological examination before full dose infusion to avoid complications. (+info)
The development and compensation of biliary cirrhosis in interleukin-6-deficient mice.
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In an effort to understand the role of IL-6/gp130 signaling in chronic liver injury, IL-6 deficient (IL-6(-/-)) and wild-type control (IL-6(+/+)) mice were subjected to bile duct ligation (BDL) for 12 weeks. This maneuver causes chronic biomechanical stress and liver injury, fueling sustained biliary epithelial and hepatocyte proliferation. By 12 weeks after BDL, IL-6(-/-) mice develop significantly higher total serum bilirubin levels (23.2 +/- 2.3 versus 14.9 +/- 2.1 mg/dl, P < 0.0001; delta bilirubin subfraction 16.7 +/- 4.0% versus 9.2 +/- 1.8%; P < 0.002), and the majority (15/18) show "black" gallbladder bile, compared to IL-6(+/+) mice (5/16; P < 0.003). The IL-6(-/-) mice also cannot sustain the compensatory liver mass increase commonly seen with chronic obstructive cholangiopathy, because of less hepatocyte proliferation, despite a rate of hepatocyte apoptosis similar to that of IL-6(+/+) mice. Moreover, IL-6(-/-) mice show a more advanced stage of biliary fibrosis and a higher mortality rate than the IL-6(+/+) controls (51% versus 23%; P < 0.02). These phenotypic changes in the IL-6(-/-) mice are associated with decreased expression and phosphorylation of gp130 and the transcription factor STAT3, compared to IL-6(+/+) mice. Daily treatment with exogenous recombinant IL-6 for 3-6 weeks starting at 6 weeks after BDL significantly lowers the serum total bilirubin in both groups. In the IL-6(-/-) mice, exogenous IL-6 treatment also increases the level of gp130 protein expression and completely reverses the loss of liver mass by increasing the hepatocyte proliferation. In conclusion, IL-6 appears to contribute to biliary tree integrity and maintenance of hepatocyte mass during chronic injury. (+info)