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Biomedical subjects

I L Kron

Publications and source records attributed to I L Kron.

At least 37 records · Page 2Linked to original sources
PubMed2001

An adenosine A2A agonist, ATL-146e, reduces paralysis and apoptosis during rabbit spinal cord reperfusion.

BACKGROUND: We hypothesized that systemic ATL-146e, an adenosine A(2A) agonist, would decrease spinal cord reperfusion inflammatory stress and inhibit apoptosis and that these effects would correlate with improved neurologic functional outcome. METHODS: Thirty rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group of animals (n = 14) received 0.06 microg/kg per minute of ATL-146e infused intravenously for 3 hours, beginning 15 minutes before reperfusion. A second group of animals (n = 16) underwent spinal cord ischemia with saline vehicle alone and served as ischemic controls. Animals (n = 9, 11) from each group survived for 48 hours and assessed for neurologic impairment with the Tarlov (0-5) scoring system. Four animals from each group were humanely killed at the end of the 3-hour treatment period, and the remainder killed after 48 hours' survival. In all animals, lumbar spinal cord tissue specimens were frozen for subsequent Western blot analysis of heat shock protein 70 (HSP 70), and for the p85 fragment of poly (ADP-ribose) polymerase (PARP). Neuronal viability indices were determined at 48 hours with hematoxylin and eosin staining. RESULTS: There was improvement in neurologic function in rabbits receiving ATL-146e (P <.001) compared with ischemic controls. At the end of the 3-hour treatment period there was a 46% (P <.05) decrease in HSP 70 expression in the ATL-146e group compared with the control group, but no difference in PARP expression. At 48 hours, there was no difference between control and ATL-146e groups in HSP 70 expression, but there was a 65% (P <.05) reduction in PARP in the spinal cords of animals that had received ATL-146e. There was a significant improvement in neuronal viability indices in animals receiving ATL-146e compared with ischemic controls (P <.05). CONCLUSIONS: Systemic ATL-146e infusion during reperfusion after spinal cord ischemia results in preservation of hindlimb motor function. There is evidence of decreased spinal cord inflammatory stress immediately after treatment with ATL-146e as indicated by reduced HSP 70 induction. Treatment with ATL-146e is associated with a reduction in neuronal apoptosis as suggested by a substantial decrease in the fragmentation of PARP at 48 hours. These results suggest that inflammation during reperfusion and subsequent apoptosis contribute to paralysis after restoration of blood flow to the ischemic spinal cord.

Animals↗
PubMed2000

Content of thoracic residency training and its relevance to the practice of medicine.

BACKGROUND: The Thoracic Surgery Directors Association (TSDA) curriculum book provides learning objectives for a thoracic surgery residency. Our purpose was to evaluate the relevance of these objectives through feedback from recent graduates. METHODS: Graduates of multiple TSDA programs were mailed a 50-item questionnaire. Survey items were objectives from the TSDA curriculum book representing six areas of thoracic surgery. Graduates rated each objective for adequacy of instruction and relevance to their current practice on Likert-type scales. RESULTS: Two hundred twenty-eight surveys were included in the analysis. Despite excellent operating room education, graduates across subspecialty lines reported the need for improved education in "nonoperative" subjects. Graduates practicing cardiac surgery reported little relevance of their general thoracic educational experience. Conversely, graduates practicing general thoracic surgery expressed the need for more/better educational experiences in thoracic oncology and esophageal surgery. CONCLUSIONS: Contemporary thoracic surgical education can be improved. A strong need for improvement exists in the teaching of "nonoperative" subjects. As graduates elect careers in thoracic subspecialties, a need exists to align thoracic surgery educational experiences with ultimate career goals of residents.

Curriculum↗
PubMed2000

Retrograde perfusion with a sodium channel antagonist provides ischemic spinal cord protection.

BACKGROUND: Neuronal voltage-dependent sodium channel antagonists have been shown to provide neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a neuronal voltage-dependent sodium channel antagonist, would provide protection during prolonged spinal cord ischemia. METHODS: In a rabbit model, spinal cord ischemia was induced for 45 minutes. Six groups of animals were studied. Controls (group I, n = 8) received no intervention during aortic cross-clamping. Group II (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg). Group IV (n = 8) received retrograde infusion of room temperature saline (22 degrees C) only. Group V (n = 8) and group VI (n = 9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion rate: 0.8 mL x kg(-1) x min(-1) during the ischemic period). Mean arterial blood pressure was monitored continuously. Animals were allowed to recover for 24 hours before assessment of neurologic function using the Tarlov scale. RESULTS: Tarlov scores (0 = complete paraplegia, 1 = slight lower limb movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop) were as follows (mean +/- SEM): group I, 0.50 +/- 0.50; group II, 0.25 +/- 0.46; group IV, 1.63 +/- 0.56; group V, 4.13 +/- 0.23; and group VI, 4.22 +/- 0.22 (p < 0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean arterial blood pressure were observed. All animals in group III became profoundly hypotensive and died before the conclusion of the 45-minute ischemic time. CONCLUSIONS: Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significant protection during prolonged spinal cord ischemia.

Animals↗
PubMed2000

Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation.

BACKGROUND: Reperfusion injury after pulmonary transplantation can contribute significantly to postoperative pulmonary dysfunction. We hypothesized that posttransplantation reperfusion injury would result in an increase in both in-hospital mortality and morbidity. We also hypothesized that the incidence of reperfusion injury would be dependent upon the cause of recipient lung disease and the interval of donor allograft ischemia. METHODS: We performed a retrospective study of all lung transplant recipients at our institution from June 1990 until June 1998. One hundred patients received 120 organs during this time period. We compared two groups of patients in this study: those experiencing a significant reperfusion injury (22%) and those who did not (78%). RESULTS: In-hospital mortality was significantly greater in patients experiencing reperfusion injury (40.9% versus 11.7%, p < 0.02). Posttransplantation reperfusion injury also resulted in prolonged ventilation (393.5 versus 56.8 hours, p < 0.001) and an increased length of stay in both the intensive care unit (22.2 versus 10.5 days, p < 0.01) and in the hospital (48.8 versus 25.6 days, p < 0.03). The incidence of reperfusion injury could not be attributed to length of donor organ ischemia (221.5 versus 252.9 minutes, p < 0.20). The clinical impact of reperfusion injury was significantly greater in patients undergoing transplantation for preexisting pulmonary hypertension (6/14) than those with chronic obstructive pulmonary disease or emphysema alone (6/54) (42.9% versus 11.1%, p < 0.012). CONCLUSIONS: Clinically significant pulmonary reperfusion injury increased in-hospital mortality and morbidity resulting in prolonged ventilation, length of stay in the intensive care unit, and cost of hospitalization. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia but increased with the presence of preoperative pulmonary hypertension. These findings suggest that recipient pathophysiology and donor allograft quality may play important roles in determining the incidence of reperfusion injury.

Female↗
PubMed2000

Aprotinin improves pulmonary function during reperfusion in an isolated lung model.

BACKGROUND: We hypothesized that the use of aprotinin would ameliorate the reperfusion injury observed after lung transplantation because of a reduction in the inflammatory response. METHODS: We used an isolated, whole blood-perfused, ventilated rabbit lung model to study the effects of aprotinin during reperfusion. The control animals (group A, n = 8) underwent lung harvest after pulmonary arterial prostaglandin E1 injection and Euro-Collins preservation flush before saline storage for 18 hours at 4 degrees C. The experimental groups received either a low dose (3,000 KIU/mL; group B, n = 8) or a high dose (10,000 KIU/mL; group C, n = 8) of aprotinin added to the pulmonary flush before storage. Each lung was reperfused at 37 degrees C at a rate of 60 mL/min. RESULTS: The arterial partial pressure of oxygen values of group B (low-dose aprotinin) were significantly higher than those of group A (control) after 10 minutes of reperfusion (69.19 +/- 5.69 mm Hg versus 264.30 +/- 48.59 mm Hg, respectively, p = 0.001). Similar results were recorded at 20 and at 30 minutes of reperfusion. Similarly, after 10 minutes of reperfusion, the differences between groups A and C were 69.19 +/- 5.69 mm Hg versus 235.91 +/- 28.63 mm Hg, respectively (p = 0.001). CONCLUSIONS: The addition of aprotinin to the Euro-Collins pulmonary flush significantly improves arterial oxygenation in the early reperfusion period. The enhanced oxygenation suggests that aprotinin may offer protection against early reperfusion injury.

Animals↗
PubMed2000

Sodium nitroprusside mitigates oleic acid-induced acute lung injury.

BACKGROUND: Acute lung injury (ALI) is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Oleic acid (OA) creates a significant ALI that physiologically mimics human adult respiratory distress syndrome (ARDS). It has been hypothesized that pulmonary vasodilatation may improve ALI. Studies in our laboratory using this model and nitric oxide (NO) have shown that NO inhalation is detrimental and worsens the effects of OA. We studied the effect of pretreatment with a potent vasodilator, sodium nitroprusside (SNP), on ALI induced by OA in an isolated lung model. We hypothesized that pretreatment with SNP will worsen pulmonary hypertension and oxygenation in OA-induced ALI, similar to the effects seen with inhaled NO in this model. METHODS: Rabbit heart lung blocks were isolated, flushed in vivo, harvested, immediately perfused with whole blood, and ventilated with 50% oxygen. Pulmonary artery pressure was determined every 15 seconds for 90 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, 60, and 90 minutes after initiation of OA infusion. Four groups were studied: saline control (SC), oleic acid control (OAC; 20-minute infusion of 50% OA/ethanol into pulmonary circulation), SNP control (NPC; 10 microg/ kg/min SNP infused without subsequent OA infusion), and SNP treatment (NPRx); 10 microg/kg/min SNP infused before OA/ethanol. Pulmonary artery pressure (PAP), oxygenation (arterio-venous oxygen difference [AVO2], compliance (CPL), and wet/dry lung weight were determined. RESULTS: No significant differences were found between the NPRx group and SC. Pretreatment with SNP eliminated the detrimental effects of OA infusion. CONCLUSIONS: Contrary to our hypothesis, pretreatment with SNP eliminates the decrease in oxygenation and increase in lung weight, and ameliorates pulmonary hypertension in our isolated lung model of OA-induced ALI.

Animals↗
PubMed2000

Hypothermic retrograde venous perfusion with adenosine cools the spinal cord and reduces the risk of paraplegia after thoracic aortic clamping.

OBJECTIVE: We evaluated the utility of retrograde venous perfusion to cool the spinal cord and protect neurologic function during aortic clamping. We hypothesized that hypothermic adenosine would preserve the spinal cord during ischemia. METHODS: Six swine (group I) underwent thoracic aortic occlusion for 30 minutes at normothermia. Group II animals underwent spinal cooling by retrograde perfusion of the paravertebral veins with hypothermic (4 degrees C) saline solution during aortic occlusion. The spinal cords of group III animals were cooled with a hypothermic adenosine solution in a similar fashion. Intrathecal temperature was monitored and somatosensory evoked potentials assessed the functional status of spinal pathways. RESULTS: Spinal cooling without systemic hypothermia significantly improved neurologic Tarlov scores in group III (4.8 +/- 0.2) and group II (3.8 +/- 0.4) when compared with group I scores (1.3 +/- 0.6) (P <.001). Furthermore, 5 of the 6 animals in group III displayed completely normal neurologic function, whereas only one animal in group II and no animals in group I did (P =.005). Somatosensory evoked potentials were lost 10.6 +/- 1.4 minutes after ischemia in group I. In contrast, spinal cooling caused rapid cessation of neural transmission with loss of somatosensory evoked potentials at 6.9 +/- 1.2 minutes in group II and 7.0 +/- 0.8 minutes in group III (P =.06). Somatosensory evoked potential amplitudes returned to 85% of baseline in group III and 90% of baseline in group II compared with only 10% of baseline in group I (P =.01). CONCLUSIONS: We conclude that retrograde cooling of the spinal cord is possible and protects against ischemic injury and that adenosine enhances this effect. The efficacy of this method may be at least partly attributed to a more rapid reduction in metabolic and electrical activity of the spinal cord during ischemia.

Adenosine↗
PubMed2000

The safety of combined cardiac and vascular operations: how much is too much?

OBJECTIVE: The purpose of this study was to identify factors correlating with a poor outcome following combined cardiac and vascular procedures. METHODS: We reviewed 45 consecutive patients undergoing combined cardiac and vascular operations. These included cardiac/CEA (n=27), cardiac/AAA (n=13), cardiac/AAA/one other vascular reconstruction (n=4), and cardiac/renal artery bypass (n=1). Group I included all patients with no morbidity or mortality (n=41) and Group II included patients who died or suffered significant morbidity (stroke, renal failure) (n=4). RESULTS: Overall mortality was 4.4% (2/45). These two patients underwent cardiac surgery combined with two additional vascular procedures (cardiac/AAA/other). In patients undergoing cardiac/CEA or cardiac/AAA, there were no deaths and one stroke (contralateral to CEA). Group II had significantly decreased ejection fraction (39%+/-6% vs 52%+/-1%) and an increased number of procedures (2.75 vs 2.04). CONCLUSIONS: Combined cardiac surgery and vascular reconstruction can be performed safely. However, multiple vascular reconstructions or the presence of decreased ejection fraction increased operative risk.

Aged↗
PubMed2000

Intensive care is cost-effective in carotid endarterectomy.

The purpose of this study was to analyze the utilization, cost profile, and predictors of intensive care unit (ICU) services after carotid endarterectomy. A retrospective medical record review of all patients undergoing isolated carotid endarterectomy by a vascular surgery service at one university hospital during a 12-month period was performed. Eighty-four patients undergoing 91 carotid endarterectomies were identified for review. All carotid endarterectomy patients at the authors' institution were routinely admitted to an ICU postoperatively. Sixty-five of the 91 patients (71.4%) required ICU interventions, the majority of which were intravenous antihypertensive therapy. There were no deaths in the group. There was one non-fatal stroke (1.1%), and one non-fatal myocardial infarction (1.1%). There were three reoperations (3.3%): two for hematoma and one for a change in neurological status. One patient required reintubation. Five of the six major adverse events after carotid endarterectomy occurred within 12 hours postoperatively. No preoperative factors predicted a significant risk for complications following carotid endarterectomy. There is no reliable predictor that carotid endarterectomy patients will require postoperative interventions or develop adverse outcomes. Mandatory intensive care immediately after carotid endarterectomy upholds high safety standards, avoids the uncertainty of preoperative ICU planning, and avoids the high cost of a recovery room stay to determine the need for intensive care. In addition, costs may be further reduced as the ICU length of stay may be decreased if there are no necessary interventions or complications after 12 hours of intensive care.

Aged↗
PubMed2000

Early carotid endarterectomy after stroke.

The authors sought to determine if patients with stroke and a high-grade carotid stenosis benefited from a delay before carotid endarterectomy. A retrospective study of 45 patients undergoing carotid endarterectomy after stroke is presented. The patients were divided into two groups: group I (early group, n = 20), composed of patients who had carotid endarterectomy less than 6 weeks after stroke, and group II (late group, n = 25), comprised of patients who had carotid endarterectomy more than 6 weeks after stroke. As assessed by cerebral angiography, 100% of patients in group I and 64% of patients in group II had carotid artery stenoses > 76% (P < 0.001). The median interval from stroke to carotid endarterectomy was 14 days in group I and 129 days in group II. There was no mortality in either group. No patients in either group demonstrated any neurological deterioration. The authors conclude that, in select patients, carotid endarterectomy may be done safely less than 6 weeks after stroke in order to avoid new events or carotid occlusion while awaiting surgery.

Aged↗
PubMed2000

Cardiac surgery.

Explore the source record for details and available documents.

Animals↗
PubMed2000

Getting funded.

Getting funded is still possible for cardiothoracic surgeons. You must have a clear hypothesis, have an organized approach, and develop excellent preliminary data. Most important, you need to apply to get funded.

Foundations↗
PubMed2000

Epidermal growth factor augments postpneumonectomy lung growth.

OBJECTIVE: Epidermal growth factor has been shown to play an important role in prenatal and postnatal lung development, but little is known about its effects on adult lung growth. We hypothesized that postpneumonectomy compensatory lung growth can be augmented by the administration of epidermal growth factor. METHODS: Adult Sprague-Dawley rats were divided into 3 groups. Sham left thoracotomy was performed in the first group (group C), left pneumonectomy in the second group (group P), and left pneumonectomy with administration of epidermal growth factor (0.2 microgram/g body weight intraperitoneally, at 72-hour intervals) in the third group (group E). The right lung growth was studied in each group 1, 3, 5, 10, and 21 days after the operation. Lung weights (in grams) and volumes (in milliliters) were expressed as a ratio to the total body weight (in kilograms) (lung weight and volume indices). Epidermal growth factor receptor was quantitated by using Western blotting. RESULTS: Using analysis of variance and contrast analysis, we noted a significant increase in lung weight index in group E versus group P rats at 3 days (3.08 vs 2.75; P =.034) and 21 days (4.62 vs 3.61; P =.006). Lung volume index was significantly increased in group E versus group P rats at 5 (16.98 vs 15.09), 10 (24.48 vs 18.81), and 21 (28.54 vs 21.01) days (P <.001). Epidermal growth factor receptor was noted to be up-regulated in the lungs of animals that received exogenous epidermal growth factor. CONCLUSIONS: This study demonstrates that administration of exogenous epidermal growth factor has a significant effect on postpneumonectomy lung growth. This process may be mediated by an up-regulation of growth factor receptor expression in the contralateral lung.

Analysis of Variance↗
PubMed2000

Retrograde venous perfusion with hypothermic saline and adenosine for protection of the ischemic spinal cord.

PURPOSE: Spinal cord injury and the resultant postoperative paraplegia are devastating complications of thoracic aortic surgery, for which no widely accepted protective interventions exist. We hypothesized that retrograde venous perfusion-cooling of the spinal cord with a hypothermic saline and adenosine solution would protect it from ischemic injury caused by thoracic aortic occlusion. METHODS: Adult domestic swine of either sex (weight range, 20 to 30 kg) were intubated and ventilated. A left thoracotomy was performed. The accessory hemiazygous vein was divided, and a catheter was inserted distally. The aorta was clamped at the left subclavian artery. The venous catheter was not used in the animals in the control group (n = 7); in the animals in the experimental group (n = 7), a cold (4 degrees C) saline and adenosine solution was infused into the accessory hemiazygous vein. After 30 minutes, the clamp and catheter were removed, and the chest was closed. A blinded observer evaluated the animals' hind-leg motor activity 24 hours later. The Tarlov scale was used: 0, complete paralysis; 1, minimal movement; 2, stands with assistance; 3, stands alone; 4, weak walk; 5, normal gait. The animals' rectal temperatures were measured at the end of the experiment, and blood pressure was measured throughout. Two other groups were studied to assess the effect of the intervention on spinal cord temperature. RESULTS: The animals in the control group had a mean Tarlov score of 1.7 +/- 0.6; the animals in the experimental group had a mean Tarlov score of 4.9 +/- 0.1 (P <.01). The animals in the experimental group had a significantly greater drop in spinal cord temperature than those in the control group (4. 05 +/- 0.6 degrees C vs 0.58 +/- 0.12 degrees C; P <.01). No significant difference in rectal temperatures was found, nor did any arrhythmias or hypotensive episodes occur in either group. Perfusion of the spinal cord was confirmed with angiography by using this approach. CONCLUSION: Retrograde venous perfusion-cooling of the spinal cord with a hypothermic saline and adenosine solution protects the cord from ischemic injury caused by clamping of the thoracic aorta.

Adenosine↗
PubMed2000

Does the additive risk of mitral valve repair in patients with ischemic cardiomyopathy prohibit surgical intervention?

OBJECTIVE: To assess the surgical risk of additional mitral valve repairs in patients with ischemic cardiomyopathy. SUMMARY BACKGROUND DATA: Severe mitral regurgitation in patients with ischemic cardiomyopathy increases the death rate and symptomatic status. The 1-year survival rate for medical therapy in this subset of patients is less than 20%. Transplantation is usually not feasible because of donor shortage and death while on the waiting list. METHODS: To assess additive risk, a retrospective chart review from 1993 to 1998 was performed comparing patients with ischemic cardiomyopathy (ejection fraction [EF] <25%) and severe mitral regurgitation undergoing mitral valve repair and coronary artery bypass graft operations with patients with an EF of <25% undergoing coronary artery bypass graft alone. These groups were also compared with 140 patients receiving heart transplants since 1993 (group 3). RESULTS: The overall hospital death rate for group 1 was 6.3%. The one death occurred 2 weeks after surgery secondary to sepsis. This was not significantly different from the death rate of 4.1% in group 2. In group 1, there were two deaths at 1 year (87% survival rate), one related to heart failure. One patient was New York Heart Association (NYHA) class IV at 1 year; the remainder of patients were NYHA class I-II. These results were not significantly different than the 8% death rate noted with transplantation. There was no change in EF and minimal residual mitral regurgitation in group 1 based on postoperative transesophageal echocardiography, whereas group 2 had an average 11.7% improvement in EF. CONCLUSIONS: Previously, severe mitral regurgitation in the setting of ischemic cardiomyopathy has been associated with poor survival. In these authors' experience, repairing the mitral valve along with coronary artery bypass grafting does not increase the surgical risk, yields improvement in symptomatic status, and compares favorably to coronary artery bypass grafting alone and cardiac transplantation. However, the lack of change in EF in these patients probably represents an overestimation of the EF before surgery secondary to severe mitral regurgitation.

Cardiomyopathy, Dilated↗