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Biomedical subjects

T L Hooper

Publications and source records attributed to T L Hooper.

At least 19 recordsLinked to original sources

Cerebral embolisation during modern cardiopulmonary bypass.

OBJECTIVES: Cerebral microembolisation still occurs during cardiopulmonary bypass and may cause both stroke and postoperative cognitive impairment. We investigated the frequency of cerebral embolisation during coronary artery bypass surgery with modern cardiopulmonary bypass and related these to ascending aortic atherosclerosis. METHODS: Transcranial Doppler monitoring for cerebral embolisation to both middle cerebral arteries was performed in 65 patients undergoing coronary artery surgery with non-pulsatile alpha-stat hypothermic bypass. Epicardial ultrasound imaging of ascending aortic atherosclerosis was performed in 14 patients. RESULTS: Thirty patients (56.9%) had more than 200 emboli entering the middle cerebral artery territories during surgery; most at the start of bypass and during defibrillation. Readjustment of aortic clamps and aortic cannulation also caused a large number of emboli which were probably particulate. Aortic disease was mild (mean plaque thickness 1 mm, interquartile range 0.9-1.2 mm) and did not relate to the number of cerebral emboli produced by aortic manipulation. CONCLUSIONS: Cerebral embolisation remains common during coronary surgery despite advances in filter and bypass pump technology. Aortic manipulation and clamping was associated with emboli but epicardial ultrasound imaging was of little help in its prediction.

Adult↗

Cerebral injury during cardiopulmonary bypass: emboli impair memory.

OBJECTIVES: Cognitive deficits occur in up to 80% of patients after cardiac surgery. We investigated the influence of cerebral perfusion and embolization during cardiopulmonary bypass on cognitive function and recovery. METHODS: Cerebrovascular reactivity was measured in 70 patients before coronary operations in which nonpulsatile bypass was used. Throughout the operations, middle cerebral artery flow velocity and embolization were recorded by transcranial Doppler and regional oxygen saturation was recorded by near-infrared spectroscopy. Cognitive function was measured by a computerized battery of tests before the operation and 1 week, 2 months, and 6 months after surgery. Elderly patients undergoing urologic surgery served as controls. RESULTS: Cerebrovascular reactivity was impaired preoperatively in 49 patients. Median (interquartile range) regional cerebral oxygen saturation fell during bypass by 10% (6%-15%), indicating increased oxygen extraction, whereas mean middle cerebral flow velocity increased significantly by a median of 6 cm/s (both P <.0001, Wilcoxon), suggesting increased arterial tone. More than 200 emboli were detected in 40 patients, mainly on aortic clamping and release, when bypass was initiated, and during defibrillation. Cognitive function deteriorated more in patients having cardiopulmonary bypass than in control patients having urologic operations but recovered in most tests by 2 months. Measures of cerebral perfusion (poor cerebrovascular reactivity, low arterial pressures, and flow velocity in the middle cerebral artery) predicted poor attention at 1 week (r = 0.3, P <.01, Spearman). Emboli were associated with memory loss (r = 0.3, P <.02, Spearman). CONCLUSIONS: Cognitive deficits were common after cardiopulmonary bypass. Occult cerebrovascular disease was more severe than expected and predisposed to attention difficulties, whereas emboli caused memory deficits. We believe this to be the first report of differing cognitive effects from emboli and hypoperfusion.

Aged↗

24-hour lung preservation: simplified versus conventional University of Wisconsin solution in a porcine model.

BACKGROUND: Experimentally, the University of Wisconsin solution (UW) has been shown to be superior to the EuroCollins solution (EC) for lung graft preservation. We showed previously that the inclusion of the trisaccharide raffinose as an impermeant in the UW is largely responsible for this superiority. In this study, we used a new porcine model of isolated lung reperfusion to evaluate the use of a simple solution of phosphate-buffered raffinose (PBr) for lung preservation. METHODS: Lungs were stored for 24 hr at 4 degrees C after a single pulmonary artery flush with either UW (n = 5) or PBr (n = 5) solution. Left lungs were ventilated with room air and reperfused for 4 hr by venovenous extracorporeal circulation from a support animal. Controls (n = 5) were flushed with UW and reperfused without storage. RESULTS: Control lungs performed better than those stored in either solution in terms of oxygenation (P = 0.034) and airway pressure (P = 0.032). There were no significant differences between the two stored groups for any parameters. Data for stored lungs after 4 hr of reperfusion (means with 95% confidence intervals) include oxygenation (mm Hg): control 101.6 (14.5), UW 85.2 (14.5), PBr 75.0 (14.5); blood flow (ml/ min): control 572 (90), UW 466 (90), PBr 468 (90); peak airway pressure (mm Hg): control 15.9 (3.0), UW 21.0 (3.0), PBr 22.6 (3.0); pulmonary artery pressure (mm Hg): control 17.5 (3.2), UW 22.3 (2.9), PBr 24.5 (2.9). Graft edema (percentage tissue water): control 86.4 (0.8), UW 89.9 (1.8), PBr 89.3 (1.0). CONCLUSION: PBr is a far simpler and less expensive alternative to UW, and appears to provide a similar level of lung graft protection.

Adenosine↗

A porcine ex vivo paracorporeal model of lung transplantation.

A technique is described which allows perfusion of an isolated, ventilated pig lung with an extracorporeal veno-venous circuit from a support animal. This model is stable for up to 4 h, and avoids some of the disadvantages of alternative small animal and large animal models of lung transplantation. It may be useful in the investigation of factors affecting lung preservation and reperfusion injury.

Animals↗

Modulation of lung reperfusion injury by nitric oxide: impact of inspired oxygen fraction.

BACKGROUND: Attempts to attenuate lung reperfusion injury by administration of inhaled nitric oxide have yielded conflicting results. We hypothesized that the inspired oxygen fraction may play an important role in determining the outcome of nitric oxide therapy. METHODS: Rat lungs were reperfused in a circuit incorporating a support animal either immediately after flushing (group A) or after 24-hr hypothermic storage (groups B-D). During the first 10 min of reperfusion, grafts were ventilated with 95% oxygen in groups A and B, 95% oxygen and 20 ppm nitric oxide in group C, and 20% oxygen and 20 ppm nitric oxide in group D. Ventilation during the subsequent 50 min of reperfusion was with 100% oxygen only, in all groups. RESULTS: Graft function in group B was poor compared to group A in terms of blood flow and pulmonary artery and peak airway pressures. In group C, although 5 out of 10 grafts functioned at control levels, the remainder performed poorly. Function in group D, on the other hand, was uniformly good. CONCLUSIONS: Inhaled nitric oxide can prevent lung reperfusion injury, but this effect may be compromised by concurrent ventilation with high oxygen concentrations.

Administration, Inhalation↗

Cardiomyoplasty: the benefits of electrical prestimulation of the latissimus dorsi muscle in situ.

BACKGROUND: Ischemic damage in the latissimus dorsi muscle may limit the success of cardiomyoplasty. Electrical prestimulation of the muscle in situ is known to enhance thoracodorsal perfusion to the distal latissimus dorsi muscle immediately after grafting. In this study we asked whether prestimulation was also beneficial under typical postoperative conditions. METHODS: Ten sheep were randomly assigned to two equal groups. In one group the latissimus dorsi muscle was stimulated continuously in situ at 2 Hz for 2 weeks; in the other group the muscle was not stimulated. Regional blood flows in the muscle were determined sequentially (1) under baseline conditions, (2) immediately after surgical mobilization, handling, and reattachment at 80% of the resting length, and (3) after 5 days. RESULTS: Manipulation of the unstimulated muscle resulted in an acute global reduction in blood flow with no improvement after 5 days. The distal region was most severely affected (26.2%+/-4.2% of baseline blood flow). Electrical prestimulation significantly reduced regional blood flow under baseline conditions but rendered the whole muscle more resistant to the surgical manipulations; blood flow was significantly better-preserved immediately afterwards, and there was complete recovery to baseline levels after 5 days. CONCLUSIONS: Electrical prestimulation of the latissimus dorsi muscle in situ reduces the acute distal ischemia caused by surgical manipulations, and promotes subsequent recovery of blood flow to baseline levels after a few days. Use of a prestimulated graft may therefore improve the outcome of skeletal muscle cardiac assistance.

Animals↗

Quantification of early damage in latissimus dorsi muscle grafts.

Acute damage in the latissimus dorsi muscle may account for variable clinical results following dynamic cardiomyoplasty and an ischemic cause has been suggested. Using established techniques, we set out to demonstrate and to quantify the acute muscle damage in a rodent model. The left latissimus dorsi muscle of 5 Sprague-Dawley rats was mobilized on its thoracodorsal vascular pedicle, thus interrupting the regional blood supply to its distal part. The undisturbed contralateral muscle served as a matched control. After 24 hours, the muscle was excised and divided into proximal, middle, and distal thirds. Damage was graded histologically and quantified by nitroblue tetrazolium macrohistochemistry. Both methods of assessment correlated well (r=-0.936; P < 0.001) and demonstrated significant damage, principally in the middle and the distal regions of the ischemic muscles. Therefore, the rodent model appears to be useful for investigating the pathogenesis and prevention of acute ischemic damage in the latissimus dorsi graft under conditions resembling the clinical scenario.

Animals↗

Controlled reperfusion protects lung grafts during a transient early increase in permeability.

BACKGROUND: We have previously shown that an initial 10-minute period of low-pressure reperfusion prevents the lung graft dysfunction that follows physiologic-pressure reperfusion. Possible mechanisms were investigated in this study. METHODS: Rat lungs were reperfused ex vivo using a parabiotic animal after 0-hour (groups A through C) or 24-hour (groups D through G) storage. Reperfusion pressure was either physiologic (groups A through D) or reduced by 50% for a specified time (groups E through G). The duration of reperfusion was 5 minutes (groups A, D, and E), 10 minutes (groups B and F), or 30 minutes (groups C and G), at which time endothelial permeability was measured through iodine 125-labeled albumin leakage and neutrophil sequestration through tissue myeloperoxidase activity. RESULTS: Graft function in group D deteriorated rapidly, whereas groups E through G performed at control levels. Albumin leakage was significantly elevated in group D; with controlled reperfusion, it was elevated after 5 minutes (group E) but had returned to baseline at 10 minutes (group F) and 30 minutes (group G). Myeloperoxidase levels were not significantly different between groups. CONCLUSIONS: Endothelial permeability is transiently elevated in the early phase of lung graft reperfusion. Initial low-pressure reperfusion may be protective by preventing irreversible edema formation during this period.

Animals↗

Nitroglycerine reduces neutrophil activation and acute damage in latissimus dorsi muscle grafts.

BACKGROUND: Damage to the latissimus dorsi muscle (LDM) may jeopardize a successful outcome to dynamic cardiomyoplasty. We and others have demonstrated muscle damage in LDM in various species including humans. Ischemia is now recognized to be an important contributory factor. We postulated that glyceryl trinitrate, a nitric oxide donor, might protect against ischemic endothelial dysfunction and so reduce resultant muscle damage. METHODS: In 20 adult rats the left LDM was mobilized on its thoracodorsal neurovascular pedicle and maintained as an orthotopic graft. Half of the animals received glycerol trinitrate intraoperatively and postoperatively for 24 hours. The other half served as untreated controls. Each group was further subdivided into two groups (n = 5 in each): animals in which the LDM was excised after 4 hours for myeloperoxidase studies, and animals in which the LDM was excised at 24 hours for analysis of muscle damage by histology and enzyme macrohistochemistry. Blood samples were taken at 24 hours for assay of plasma nitrite and nitrate as nitric oxide metabolites. RESULTS: Glycerol trinitrate-treated animals had higher plasma nitric oxide metabolite levels after 24 hours (after nitrate reductase treatment, total nitrite, 78.3+/-11.8 nmol/mL, mean +/- SEM) than controls (42.1+/-3.7 nmol/ mL, p = 0.008). The proportion of viable LDM in glycerol trinitrate-treated animals was greater than in untreated animals, mainly in the middle and distal regions of the graft (middle region, 96.3%+/-0.5% versus 75.7%+/-4.1%, p<0.001; distal region, 94.4%+/-0.8% versus 40.9%+/-3.1%, p<0.001). Macrohistochemical findings correlated well with the histologic findings. Myeloperoxidase activity (U/g) was markedly lower in glycerol trinitrate-treated LDMs, mainly in the distal part of the graft (glycerol trinitrate versus control, 20.5+/-2.1 versus 40.9+/-3.1 U/g, p<0.001). CONCLUSIONS: Glycerol trinitrate significantly reduced acute damage to the distal two-thirds of the mobilized LDM, possibly by modifying leukocyte activation and endothelial dysfunction associated with ischemic injury.

Animals↗

Observation and basis of improved blood flow to the distal latissimus dorsi muscle: a case for electrical stimulation prior to grafting.

OBJECTIVE: Dynamic cardiomyoplasty, using a functional graft of the latissimus dorsi muscle, has shown promise as a treatment for selected patients with advanced heart failure. The success of this approach depends on maintaining the viability of the muscle, whose distal portion is susceptible to ischaemic damage. We investigated the effects of surgical mobilization on regional muscle blood flow and the influence of electrical stimulation of the muscle. METHODS: Ten sheep were randomly assigned to two equal groups. In one group, the latissimus dorsi muscle was stimulated continuously in situ at 2 Hz for two weeks; in the other group, the muscle was not stimulated. Regional blood flows in the muscles were determined by a fluorescent microsphere technique. Serial measurements were made (a) under baseline conditions before intervention, (b) with the thoracodorsal artery occluded and (c) after interruption of the perforating collateral arteries. RESULTS: Surgical mobilization of the unstimulated latissimus dorsi muscles had little effect on blood flow in the proximal region, which remained at 93.1 +/- 16.9% of baseline (mean +/- SEM). The distal region was rendered significantly more ischaemic (55.8 +/- 13.5% of baseline, p < 0.002 compared to the proximal region). Electrical prestimulation abolished any significant proximodistal gradient in blood flow and improved distal muscle perfusion following mobilization (proximal vs. distal: 75.0 +/- 8.8 vs. 63.0 +/- 10.9%; p > 0.4). CONCLUSIONS: Distal muscle ischaemia occurred when the entire latissimus dorsi muscle was acutely elevated on the thoracodorsal pedicle alone. Electrical prestimulation of the muscle in situ improved the thoracodorsal perfusion of the distal muscle by abolishing the proximal-to-distal gradient in flow, with a substantial benefit to distal flow after mobilization. Although electrical stimulation is known to induce vascular proliferation, we argue that this effect of stimulation is brought about mainly by enhancement of the flow through anastomotic connections between proximal and distal arterial territories.

Animals↗

Morphological and functional evidence, and clinical importance, of vascular anastomoses in the latissimus dorsi muscle of the sheep.

Mobilisation of the latissimus dorsi muscle as a functional graft necessarily involves division of perforating arteries that enter the distal portion of the muscle, rendering it vulnerable to ischaemic damage when the muscle is stimulated electrically. Using a fluorescent microsphere technique we showed that the blood flow contributed by the thoracodorsal artery decreases in a proximal-to-distal direction, and that of the perforating arteries in a distal-to-proximal direction, but for neither does the flow decline to zero. This is consistent with earlier reports of anastomotic connections between the 2 arterial territories. We went on to use fluorescence microscopy to demonstrate the existence of these vascular anastomoses, the first such evidence obtained under physiological conditions of pressure and flow. In clinical applications, the existence of anastomotic connections offers the prospect of maintaining flow to the distal part of the grafted muscle without the delays inherent in neovascularisation procedures.

Animals↗

Acute muscle damage in latissimus dorsi grafts mobilized for cardiac assist: is vasospasm an important factor?

BACKGROUND: Muscle damage in latissimus dorsi grafts is known to occur following surgical mobilization for cardiomyoplasty. It is believed that ischemia may be a contributory factor. We tested the hypothesis that surgical manipulation of the muscle graft resulted in vasospasm of the intramuscular arteries that compromised muscle viability by examining the effects of vasodilators in the early ischemic period. METHODS: Rat latissimus dorsi muscles were mobilized from all truncal attachments with preservation of the thoracodorsal neurovascular pedicle. Undisturbed contralateral muscles served as controls. After 24 hours, regional analysis of muscle viability was performed by enzyme macrohistochemistry and histologic assessment. The experimental interventions in four randomized groups (n = 5 each) included: group A, control; group B, topical papaverine (1%); group C, intravenous hydralazine (0.5 mg/kg); and group D, intravenous verapamil (75 microg/kg). RESULTS: All mobilized muscles showed loss of viability, as compared to controls, with damage most apparent in the distal part (mobilized vs control: viable area = 56.76% [51.26-62.26] vs 98.54% [97.87-99.21]; p < 0.001). All three vasodilators failed to prevent muscle necrosis whereas papaverine appeared to aggravate the damage (papaverine vs control: viable area = 53.60% [30.73-76.47] vs 76.60% [75.02-78.18] in the middle region; p < 0.05 and 44.27% [29.53-59.01] vs 56.76% [51.26-62.26] in the distal region; p < 0.05). CONCLUSIONS: The rodent model appears to be useful for studying latissimus dorsi muscle injury. The use of vasodilators at the time of surgical mobilization of the latissimus dorsi muscle does not appear to influence the degree of early muscle damage. Topical papaverine may be detrimental to the muscle in this regard.

Administration, Topical↗

Clinical evaluation of the new Pall leucocyte-depleting blood cardioplegia filter (BC1).

It is now widely acknowledged that autologous leucocytes are inappropriately activated during cardiopulmonary bypass (CPB). Removal of these activated leucocytes has been proposed as a clinical intervention. Several papers have recently reported benefits of systemic leucocyte depletion during CPB. There is also evidence that leucocyte-depleted blood cardioplegia is advantageous in the globally ischaemic human heart transplant setting. Recently, a new leucocyte-depleting filter for blood cardioplegia has been developed (Pall, BC1). In this paper, we report on the safety and efficiency of this device in the clinical situation. Fourteen patients undergoing routine cardiac surgery were recruited into this study. The BC1 blood cardioplegia filter was found to be an efficient leucocyte-depleting device, removing in excess of 70% (p = 0.001) of white blood cells, on average, from up to 5.3 litres of blood cardioplegia. The filter removed a small proportion of platelets (typically 11.3%), however, this was not statistically significant and no bleeding problems were encountered. Red cell removal was negligible and was not statistically significant, and no evidence of haemolysis was noted. The filter offered a very low resistance to flow with a mean pressure drop (deltaP) of 10.8 mmHg at a mean flow rate of 315 ml/min. We conclude that the Pall BC1 filter is a safe and efficient device for use with blood cardioplegia.

Aged↗

Pulmonary graft preservation: a worldwide survey of current clinical practice.

BACKGROUND: Flush perfusion of pulmonary grafts with cold modified EuroCollins solution supplemented by prostaglandin treatment was introduced clinically 10 years ago. Primary graft failure remains a major cause of morbidity and death after lung transplantation. During the last decade, much experimental work has led to reports of alternative storage solutions, differing storage conditions, and pharmacologic interventions that improve pulmonary graft performance. It is unclear how these findings have influenced current clinical practice. METHODS: A worldwide survey of the 125 centers performing lung transplantation was conducted by questionnaire. RESULTS: One hundred twelve replies were received (90%). Most centers (n = 86) continue to use EuroCollins solution (77%), of whom 69% include prostaglandin therapy and 32% donor steroid treatment. University of Wisconsin solution (UW) is used by 15 centers (13.5%), of which 10 (67%) use prostaglandin and seven (47%) use donor steroids. Nine centers use Papworth solution and one uses donor core cooling. The volume of flush used varied widely, from 20 to 120 ml/kg, with median volumes of 60, 60, and 30 ml/kg in centers using EuroCollins, UW, and Papworth solutions, respectively. Two thirds of centers using EuroCollins solution store grafts at 0 degrees to 5 degrees C, and one third at 5 degrees to 10 degrees C. One center that uses EuroCollins solution stores grafts at 10 degrees to 15 degrees C. Centers using UW solution are evenly split at 0 degrees to 5 degrees C and 5 degrees to 10 degrees C. Most centers that use Papworth solution store grafts at 5 degrees to 10 degrees C. Only six centers use superoxide radical scavengers. The maximum ischemic period accepted by centers varies from 4 to 12 hours, with median periods of 8, 7, 6, and 6 hours for the UW, EuroCollins, Papworth, and donor core cooling centers, respectively. All but one of the UW centers (93%) expressed satisfaction with the quality of graft preservation achieved by UW solution. Only 58 of the 86 centers using EuroCollins solution (67%) were satisfied. Six of nine centers using Papworth solution were satisfied. CONCLUSIONS: There has been a trend toward the use of UW solution and a slightly warmer storage temperature. However, for most centers, graft storage techniques have changed little over the last decade.

Adenosine↗

Low-dose nitric oxide inhalation during initial reperfusion enhances rat lung graft function.

BACKGROUND: In ischemia-reperfusion injury, the production of nitric oxide by dysfunctional endothelium falls rapidly within minutes of the onset of reperfusion. Replenishment during this critical early period using inhaled nitric oxide may benefit lung grafts through modulation of vascular tone, endothelial permeability, neutrophil and platelet function, and availability of reactive oxygen species. METHODS: Rat lung grafts were flushed with 60 mL/kg cold University of Wisconsin solution and were reperfused either immediately (group I, n = 5) or after 24-hour 4 degrees C storage (groups II and III, n = 5 each), for 60 minutes in an ex vivo model incorporating a support animal. Graft ventilation was with room air. In group III, 20 parts per million inhaled nitric oxide was added during the initial 10 minutes of reperfusion, whereas in groups I and II, equivalent flows of nitrogen were added to standardize oxygen concentration. RESULTS: Compared with group I, graft function in group II was poor, with reductions in oxygenation and blood flow and elevations of mean pulmonary artery pressure, peak airway pressure, and wet to dry weight ratio. In contrast, during nitric oxide inhalation in group III, graft function improved to control levels. This improvement was subsequently sustained throughout the reperfusion period. CONCLUSIONS: Low-dose inhaled nitric oxide administration in the early phase of reperfusion of stored lung grafts can yield sustained improvement in function. There may be a role for inhaled nitric oxide in the prevention of reperfusion injury in transplanted lungs.

Animals↗

Intramural blood flow of skeletal muscle ventricles functioning as aortic counterpulsators.

BACKGROUND: Skeletal muscle ventricles (SMVs) working as aortic counterpulsators have provided long-term left ventricular assistance under experimental conditions. However, gradual deterioration of SMV pump function and rupture have been observed, and this may be related to compromised intramural blood flow during synchronized counterpulsation under systemic working conditions. METHODS: Transformed, double-layered SMVs in 6 sheep were stimulated for 3-minute periods (5 V, 30 Hz, burst duration and delay from QRS both 40% of the cardiac cycle) to work as diastolic counterpulsators in the systemic circulation at a 1:2 (SMV:heart) and 1:1 ratio, and on a mock circulation with low-pressure loading conditions at a 1:2 ratio. Thoracodorsal artery blood flow was monitored by ultrasonic flow probe, and intramural blood flow distribution was investigated by fluorescent microspheres. Thoracodorsal venous lactate concentrations were measured before and after each period of stimulation. RESULTS: Thoracodorsal artery blood flow increased significantly (p < 0.001) after stimulation. The magnitude of augmentation (89%; 95% confidence interval, 36% to 163%) was similar for all working conditions studied. Reactive hyperemia was observed after most 1:1 regimens but was rare after 1:2 regimens. A significant (p < 0.05) 15% increase in serum lactate levels was present after 1:1 regimens only. All regimens of stimulation resulted in a significant increase (p < 0.01) in blood flow to sections in the outer wall of the SMV, but a significant increase (p < 0.05) in blood flow to sections in the inner wall was observed only under low loading conditions. CONCLUSIONS: Skeletal muscle ventricles subjected to 1:1 systemic counterpulsation regimens work under partly anaerobic conditions. High loading conditions may compromise SMV inner wall blood flow.

Animals↗

Attenuation of lung graft reperfusion injury by a nitric oxide donor.

OBJECTIVE: One of the primary features of ischemia-reperfusion injury is reduced production of protective autocoids, such as nitric oxide, by dysfunctional endothelium. Administration of a nitric oxide donor during reperfusion of lung grafts may therefore be beneficial through modulation of vascular tone and leukocyte and platelet function. METHODS: Rat lung grafts were flushed with University of Wisconsin solution and reperfused for 1 hour in an ex vivo model incorporating a support animal. Group I grafts (n = 6) were reperfused immediately after explantation, group II (n = 6) and III (n = 5) grafts after 24 hours of storage at 4 degrees C. In group III, glyceryl trinitrate, a nitric oxide donor, was administered during the first 10 minutes of reperfusion at a rate of 200 micrograms/min. In an additional group (n = 5), 200 micrograms/min hydralazine was administered instead, to assess the effect of vasodilation alone. RESULTS: Graft function in group II deteriorated compared with that in group I, with significant reduction of graft effluent oxygen tension and blood flow and elevation of pulmonary artery pressure, peak airway pressure, and wet/dry weight ratio. In contrast, in group III, glyceryl trinitrate treatment improved graft function to baseline levels in all these parameters. Administration of hydralazine, meanwhile, produced mixed results with only two out of five grafts functioning at control levels. CONCLUSIONS: In this model, administration of glyceryl trinitrate to supplement the nitric oxide pathway in the early phase of reperfusion has a sustained beneficial effect on lung graft function after 24-hour hypothermic storage, probably through mechanisms beyond vasodilation alone.

Animals↗