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Biomedical subjects

A M Sadeghi

Publications and source records attributed to A M Sadeghi.

At least 37 records · Page 2Linked to original sources

Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model.

Retrograde cerebral perfusion (RCP) is a new method of cerebral protection that has been touted as an improvement over hypothermic circulatory arrest (HCA). However, RCP has been used clinically for durations and at temperatures that are "safe" for HCA alone. This study was designed to compare RCP to HCA and antegrade cerebral perfusion (ACP) deliberately exceeding "safe" limits, in order to determine unequivocally whether RCP provides better cerebral protection than HCA. Four groups of six Yorkshire pigs (20 to 30 kg) were randomly assigned to undergo 90 minutes of RCP, ACP, HCA, or HCA with heads packed in ice (HCA-HP) at an esophageal temperature of 20 degrees C. Arterial, mixed venous and cerebral venous oxygen, glucose and lactate contents; quantitative EEG; were monitored at baseline (37 degrees C); at the end of cooling cardiopulmonary bypass (20 degrees C); during rewarming (30 degrees C); and at two and four hours post intervention. Animals were recovered and were evaluated daily using a quantitative behavioral score (0 to 9). Mean behavioral score was lower in the HCA group than in the other three groups at seven days (HCA 5.8 +/- 1.1; RCP 8.5 +/- 0.2; ACP 9.0 +/- 0.0; HCA-HP 8.5 +/- 0.2, p < 0.05). Recovery of QEEG was better in the ACP group than in all others, but the RCP group had faster EEG recovery than HCA alone, although not better than HCA-HP (HCA 15 +/- 4; RCP 27 +/- 3; ACP 78 +/- 5; HCA-HP 19 +/- 3, p < 0.001). However, histopathological evidence of ischemic injury was present in 5 of 6 HCA animals and also in 4 of 6 of the HCP-HP group, but only in 1 of 6 RCP animals and in none of the ACP group. This study demonstrates that ACP affords the best cerebral protection by all outcome measures, but RCP provides clear improvement compared to HCA.

Animals↗

A new technique using somatosensory evoked potential guidance during descending and thoracoabdominal aortic repairs.

Recent work in our laboratory has demonstrated the effectiveness of somatosensory evoked potentials (SEPs) in identifying the critical intercostal arteries (CICAs) for preserving spinal cord integrity during simulated aortic aneurysm repairs in the pig. Further studies have also demonstrated increased preservation of neurological function during prolonged aortic clamping if CICAs are perfused until ligation or clipping, as opposed to transaortic identification of back-bleeding intercostals and their subsequent ligation. We have developed a technique of repair of descending thoracic and thoracoabdominal aortic aneurysms and dissections that uses these principles. Since January 1993, 26 patients have undergone repair of their aortas using this new technique and SEP directed intercostal artery ablation. There were 22 (85%) long-term survivors among 10 thoracoabdominal and 16 descending aortic repairs. All patients with uncorrected abnormal SEP recordings developed paralysis; one patient who required reimplantation of an intercostal artery island into the aortic graft had normal neurological function postoperatively. Paraplegia was seen in only one of the surviving patients, but this patient had normal intra- and postoperative SEPs (4% false negative). Our experience suggests that SEP-guided obliteration of intercostal arteries while maintaining perfusion may be a useful approach to the surgical repair of descending and thoracoabdominal aortic disease.

Adolescent↗

Evaluation of cerebral metabolism and quantitative electroencephalography after hypothermic circulatory arrest and low-flow cardiopulmonary bypass at different temperatures.

Although widely used for repair of complex cardiovascular pathologic conditions, long intervals of hypothermic circulatory arrest and low flow cardiopulmonary bypass may both result in cerebral injury. This study examines cerebral hemodynamics, metabolism, and electrical activity to evaluate the risks of cerebral injury after 60 minutes of hypothermic circulatory arrest at 8 degrees C, 13 degrees C, and 18 degrees C, compared with 60 minutes of low flow cardiopulmonary bypass at 18 degrees C. Thirty-two puppies were randomly assigned to one of four experimental groups and centrally cooled to the appropriate temperature. Serial evaluations of quantitative electroencephalography, radioactive microsphere determinations of cerebral blood flow, calculations of cerebral oxygen consumption, cerebral glucose consumption, cerebral vascular resistance, cerebral oxygen extraction, systemic oxygen metabolism, and systemic vascular resistance were done. Measurements were obtained at baseline (37 degrees C), at the end of cooling, at 30 degrees C during rewarming, and at 2, 4, and 8 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass. At the end of cooling, cerebral vascular resistance remained at baseline levels in all groups, but systemic vascular resistance was increased in all groups. Cerebral oxygen consumption became progressively lower as temperature was reduced: it was only 5% of baseline at 8 degrees C; 20% at 13 degrees C; and 34% and 39% at 18 degrees C. Quantitative electroencephalography was silent in the 8 degrees C and 13 degrees C groups, but significant slow wave activity was present at 18 degrees C. Systemic vascular resistance and cerebral oxygen consumption returned to baseline values in all groups by 2 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass, but cerebral vascular resistance remained elevated at 2 and 4 hours, not returning to baseline until 8 hours after hypothermic circulatory arrest or low flow cardiopulmonary bypass. All but two of the long-term survivors (27 of 32) appeared neurologically normal; after hypothermic circulatory arrest at 8 degrees and 18 degrees C two animals had an unsteady gait. Comparison of quantitative electroencephalography before operation and 6 days after operation showed a significant increase in slow wave activity (delta activity) after hypothermic circulatory arrest and low flow cardiopulmonary bypass at 18 degrees C, a change that suggests possible cerebral injury. Although undetected after operation by simple behavioral and neurologic assessment, significant differences in cerebral metabolism, vasomotor responses, and quantitative electroencephalography do exist during and after hypothermic circulatory arrest and low flow cardiopulmonary bypass at various temperatures and may be implicated in the occurrence of cerebral injury.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

The natural history of thoracic aortic aneurysms.

Because improved understanding of the natural history of thoracic aneurysms would enhance our ability to determine in which cases the risk of surgical treatment is justified, the rate of enlargement of thoracic aneurysms and thoracoabdominal aneurysms was studied in 67 patients by means of serial computer-generated three-dimensional reconstructions of computed tomographic scans. Patients were followed for a mean of 1.5 +/- 0.15 years (0.2 to 5.35 years) with an average interval between examinations of 0.9 +/- 0.1 year (0.2 to 5.0 years). Thirty-nine patients continue to be followed; 7 were lost to follow-up; 14 died during follow-up (4 after aneurysm rupture), and 10 underwent an operation. Indications for operation included the presence of pain, an absolute aortic diameter larger than 8 cm, an increase in aortic diameter of more than 1 cm per year, or marked irregularity of aneurysm contour. Aortic diameter and volume data were generated from the aortic silhouette obtained by tracing each computed tomographic slice with a translucent digitizing tablet. Estimated change in aortic diameter after 1 year was 0.43 cm; estimated change in aortic volume was 88.1 ml. The impact of possible risk factors on the enlargement of aneurysms was examined by analysis of variance (p < 0.05). A significantly higher rate of aneurysm expansion was found in patients with a larger aortic diameter (> 5 cm) at diagnosis (change in diameter = 0.17 cm versus 0.79 cm; change in volume = 40 ml versus 141.8 ml), and in smokers (change in diameter = 0.35 cm versus 0.70 cm; change in volume = 78.3 ml versus 120.8 ml). Changes in diameter and volume for aneurysms of different initial diameters and volumes was predicted by exponential regression by the equations: change in diameter = 0.0167 (initial aortic diameter)2.1; change in volume = 0.0356 (initial aortic volume)1.322. No correlation was noted between the rate of enlargement and age, sex, or the presence of dissection. A history of hypertension correlated with a greater aortic diameter at diagnosis but did not significantly affect the rate of enlargement.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Cerebral blood flow and metabolism in hypothermic circulatory arrest.

Although hypothermic circulatory arrest has been accepted for use in cardiovascular operations, the potential for cerebral injury exists. The mechanism of the cerebral injury remains unclear. To address these questions we studied cerebral blood flow and metabolism. Sixteen puppies were randomly assigned to undergo either 45 or 90 minutes of hypothermic circulatory arrest after perfusion/surface cooling to 13 degrees C. Cerebral blood flow, cerebral oxygen and glucose metabolism, and cerebral vascular resistance measurements were obtained at 37 degrees C, 13 degrees C, 10 minutes after reperfusion, 30 degrees C and 2 and 4 hours after hypothermic circulatory arrest. No neurologic or behavioral changes were observed in any of the long-term survivors (11/16). Metabolic and cerebral blood flow data did not differ between groups. Cerebral blood flow was significantly lower in the late postarrest measurements, whereas oxygen and glucose consumption had returned to baseline values. In the presence of low cerebral blood flow and high cerebral vascular resistance it is notable that control levels of oxygen consumption were attained by abnormally high oxygen extraction. These data strongly suggest a vulnerable interval after hypothermic circulatory arrest in which cerebral metabolism is limited by cerebral blood flow.

Animals↗

Effects of acute hypoxia and reoxygenation in a blood-perfused neonatal heart model.

Newborn (less than 4-day old) piglet hearts (n = 7) were isolated and perfused with blood from a support pig. With use of a reservoir and membrane oxygenator, each heart was perfused for 90 minutes with blood at an O2 saturation of 40% and a pH of 7.4-7.5, at a left atrial pressure of 9 mm Hg, and at an aortic root pressure of 80 mm Hg. Blood saturation was increased to 100%, and the left atrial pressure decreased to 6 mm Hg for 60 minutes. Minute work indexes were calculated for each heart before hypoxia, every 30 minutes during hypoxia, and at 30 and 60 minutes of reoxygenation. Control hearts (n = 8) were treated in an identical fashion, but O2 saturation was maintained at 100%. Myocardial function decreased in the neonatal hearts exposed to hypoxia and reoxygenation. Control hearts did not suffer any significant decrease in function. Nucleotide levels were similar in both groups at the completion of the experiment. Anaerobic metabolism was demonstrated in the hypoxic hearts by net release of lactic acid during the period of hypoxia. This model can be used to study methods of intervention in the working hypoxic neonatal heart.

Acute Disease↗

Cardiac xenotransplantation in primates.

Successful cardiac xenotransplantation would alleviate the severe shortage of donor organs that presently limits the availability of cardiac transplantation. Early attempts at human xenotransplantation achieved minimal success. However, the effectiveness of cyclosporine in nonhuman xenotransplant models has received little experimental investigation. We have therefore studied the effect of cyclosporine-based immunosuppression in primate cardiac xenograft models using cynomolgus monkey donors and baboon recipients. Donor hearts were transplanted heterotopically into the necks of recipients or in the orthotopic position. Recipients were treated with no immunosuppression (controls), cyclosporine and steroids, or cyclosporine, steroids, azathioprine, and antithymocyte globulin. Statistically significant prolongation of graft survival compared to the control group was observed in the heterotopic groups. Mean survival time of the cyclosporine-treated and steroid-treated heterotopic grafts was 61 days compared to 6 days for grafts in the control group (p = 0.01); the addition of azathioprine and antithymocyte globulin yielded a mean survival of 84 days (p less than 0.01). No significant increase in graft survival was noted in the orthotopic groups treated with either immunosuppressive regimen. Although long-term use of human xenografts as an alternative for heart replacement is not supported by these data, further investigation of the orthotopic model is clearly justified.

Animals↗

Hypothermic preservation of the heart and lungs with Collins solution: effect on cardiorespiratory function following heart-lung allotransplantation in dogs.

The effect of preserving the heart and lungs with hypothermia and Collins solution was studied in 13 mongrel dogs undergoing combined heart-lung transplantation. The five control animals who underwent an immediate transplant following Collins solution perfusion had small increases in extravascular lung water when measured 2.5 hours posttransplant as seen in a previous study. The eight animals who had hypothermic preservation following Collins solution perfusion had significantly higher extravascular lung water than controls (16.3 +/- 1.8 ml/kg in preserved animals; 11.2 +/- 1.7 ml/kg in controls p less than 0.05). The level of lung water reached at 2.5 hours postoperatively was similar to that reached with a previously reported, unacceptable preservation technique. Survival beyond this point was poor due to severe pulmonary edema. We conclude that the use of this solution, given under the experimental conditions which we describe, is not acceptable for hypothermic preservation of the heart and lungs for combined transplantation.

Animals↗

The effect of hypothermic preservation of the heart and lungs on cardiorespiratory function following canine heart-lung transplantation.

The effect of hypothermic preservation of the heart and lungs with a crystalloid solution was evaluated in 12 mongrel dogs receiving heart-lung allografts. Six animals served as controls and received an immediate heart-lung transplant. Six animals were in the experimental group and received a heart-lung transplant after 5 hours of preservation at 4 degrees C following perfusion of both organs with a crystalloid solution. Physiological function of the heart and lungs was studied for 20 hours after transplantation. While cardiac function was minimally depressed following preservation, pulmonary function testing demonstrated significantly greater increases in extravascular lung water in experimental animals, suggesting that an ischemic lung injury occurred with this preservation technique. The model allows for future evaluation of other methods of combined preservation of both the heart and lungs for transplantation.

Airway Resistance↗

Acute physiological changes following heart-lung allotransplantation in dogs.

The feasibility of clinical heart-lung transplantation requires a better understanding of the physiological consequences of the operation, heart-lung denervation, and the quality of graft preservation. An acute canine model was used to evaluate heart-lung function during the first 24 hours after transplantation. Measurements of cardiopulmonary dynamics were performed in 5 donor animals and compared sequentially after transplantation in the respective recipients. Orthotopic allotransplantation was performed on cardiopulmonary bypass with moderate hypothermia after perfusion of both the heart and lung with a clinical cardioplegic solution (4 degrees C; potassium chloride, 30 mEq/L; mannitol, 20 gm/L). Postoperatively, the animals were ventilated continuously and anesthetized. Hemodynamic variables were monitored, and measurements were made of arterial and venous oxygen, carbon dioxide, saturation, and pulmonary mechanics. Cardiac output and a derived measurement of lung water were determined. Pulmonary vascular resistance, arteriovenous shunt, resistance, and compliance were calculated. At the termination of the experiment, significant differences were observed between donor and recipient lung-water levels (7.7 +/- 0.9 ml/kg versus 12.0 +/- 3.1 ml/kg, respectively; p less than 0.05); 100% arterial oxygen tension (509 +/- 37 mm/Hg versus 227 +/- 114 mm/Hg, respectively; p less than 0.01); and pulmonary compliance (38 +/- 18 ml/cm H2O versus 11 +/- 4 ml/cm H2O, respectively; p less than 0.05). Arteriovenous shunt increased from 12.2 +/- 4 to 16.5 +/- 5% (p = 0.2). This model evaluates the technique currently employed clinically and will be used in the future to compare methods of heart-lung preservation with the goal of allowing distant heart-lung procurement.

Animals↗