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Biomedical subjects

T L Hooper

Publications and source records attributed to T L Hooper.

At least 37 records · Page 2Linked to original sources

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↗

Latissimus dorsi muscle blood flow during synchronized contraction: implications for cardiomyoplasty.

BACKGROUND: Damage in latissimus dorsi muscle flaps has been reported after clinical and experimental cardiomyoplasty, and an ischemic origin has been suggested. METHOD: In situ, preconditioned latissimus dorsi muscles in 5 sheep were stimulated in either 1:1 (muscle: heart) or 1:2 synchrony with the systolic phase of the cardiac cycle, using a burst duration of either 21% or 35% of the cycle. Thoracodorsal artery blood flow and thoracodorsal venous lactate concentrations were measured before and immediately after a 3-minute period of stimulation. RESULTS: The exercise-induced augmentation of thoracodorsal artery blood flow was significantly (p < 0.05) less with a 1:2 regimen than a 1:1 regimen, for both a 21% (88%; 95% confidence interval [CI], 55.6% to 127.3% versus 138.9%; CI, 97.6% to 188.8%) and 35% burst duration (123.2%; CI, 84.7% to 169.9% versus 167.0; CI, 120.8% to 222.6%). After cessation of stimulation, reactive hyperaemia was observed in 3 of 5 animals with 1:1 21% burst stimulation, and in 5 of 5 animals with a 35% burst duration, but was not seen after 1:2 regimens. A significant (p < 0.01) increase in thoracodorsal venous lactate levels was present after 1:1 35% burst stimulation (34.9%; CI, 9.9% to 65.6%), but lactate levels tended to fall when a 1:2 ratio was used (15.9%; CI, -3.2% to 31.5%; p < 0.1). CONCLUSIONS: One-to-one stimulation regimens may be detrimental to latissimus dorsi blood flow, and an adaptive, rather than fixed, burst duration may be preferable. These findings have important implications for the cardiomyoplasty procedure.

Animals↗

Critical importance of the first 10 minutes of lung graft reperfusion after hypothermic storage.

BACKGROUND: We have shown previously that lung graft function can be improved by achieving reperfusion with stepwise increments of perfusion pressure over 60 minutes. This study aimed to establish whether similar benefit could be achieved with a shorter, simpler protocol and different storage conditions. METHODS: Rat lungs were flushed with University of Wisconsin or modified Euro-Collins solution and reperfused for 1 hour with blood from a support animal. Grafts were reperfused immediately or after storage at 4 degrees C for 24 hours (University of Wisconsin solution) or 6 hours (Euro-Collins solution). Stored-graft reperfusion was initiated with a 0-, 5-, or 10-minute period during which reperfusion pressure was reduced by 50%. RESULTS: Stored grafts receiving 0 to 5 minutes of initial low-pressure reperfusion performed poorly, with reduced oxygenation and blood flow and elevated pulmonary artery pressure, airway pressure, and wet/dry weight ratio. In contrast, 10 minutes of initial 50%-pressure reperfusion yielded function comparable with that in controls with both storage conditions. CONCLUSIONS: An initial 10-minute period of 50%-pressure reperfusion improves the function of stored rat lung grafts, whereas 5 minutes is insufficient.

Adenosine↗

Relative importance of prostaglandin/cyclic adenosine monophosphate and nitric oxide/cyclic guanosine monophosphate pathways in lung preservation.

BACKGROUND: Modulation of vascular tone and platelet and neutrophil function through the prostaglandin/cyclic adenosine monophosphate or nitric oxide/cyclic guanosine monophosphate pathway can benefit lung graft function. The relative importance of these pathways is unclear. METHODS: Rat lung grafts (5 per group) were studied in an ex vivo reperfusion model. Group I grafts were pretreated with prostacyclin (20 ng.kg-1.min-1), flushed with cold Euro-Collins solution containing prostacyclin (200 micrograms/L), and reperfused immediately for 1 hour. Group II grafts were similarly procured but were stored at 4 degrees C for 6 hours before reperfusion. In group III, no prostacyclin therapy was used; instead, the nitric oxide donor glyceryl trinitrate (0.1 mg/mL) was added to the flush/storage solution, and the grafts were stored for 6 hours. RESULTS: Group II grafts performed poorly compared with those in group I, with substantial deterioration of oxygenation and blood flow and elevation of pulmonary artery pressure, peak airway pressure, and wet to dry weight ratio. In contrast, graft function in group III was similar to that in controls. CONCLUSIONS: Lung graft integrity after storage in Euro-Collins solution was better preserved by glyceryl trinitrate than by prostacyclin in this model.

Animals↗

Severe mitral valve dysfunction due to unsuspected granulomatous myocarditis: successful cardiac transplantation following attempted mitral valve repair.

Granulomatous involvement of the myocardium is a rapidly fatal disease of uncertain aetiology rarely diagnosed premorbidly. We report a patient who presented with mitral valve incompetence and congestive cardiac failure who underwent a successful mitral valve repair but could not be weaned from cardiopulmonary bypass. Urgent heart transplantation was successfully performed and histological studies of the explanted heart revealed granulomatous myocarditis involving the mitral subvalvular apparatus. Endomyocardial biopsy may be necessary in young patients presenting with mitral valve disease of unknown aetiology.

Adult↗

Controlled pressure reperfusion of rat pulmonary grafts yields improved function after twenty-four-hours' cold storage in University of Wisconsin solution.

BACKGROUND: Pulmonary graft recipients commonly have a degree of pulmonary hypertension. Immediate reperfusion of stored pulmonary grafts at supraphysiologic or even physiologic pressures may be detrimental to subsequent function. We wished to test the hypothesis that initial reperfusion of pulmonary grafts at low pressures may be beneficial. METHODS: We used an isolated, ventilated rat lung model, perfused by an extracorporeal veno-venous circuit from a support animal. Three groups of donor lungs (n = 5 each) were flushed with cold University of Wisconsin solution. Group I was reperfused immediately at physiologic pressure to provide control values. Group II grafts were stored at 4 degrees C for 24 hours and reperfused at physiologic pressure. Group III grafts were also stored at 4 degrees C for 24 hours but reperfused according to a protocol of reduced pressure initially, with increments every 15 minutes up to physiologic levels by 60 minutes. Grafts and support animals were ventilated with room air. Graft function was assessed over a 2-hour period with regard to oxygenation, vascular resistance, peak airway pressure, and the wet/dry weight ratio. RESULTS: Grafts in group II functioned poorly at 2 hours compared with control values: group II: oxygen tension 68 +/- 4 mm Hg; pulmonary vascular resistance 2488 +/- 675 x 10(3) dyne.sec/cm5; peak airway pressure 32 +/- 1 mm Hg wet/dry wright ratio 9.1 +/- Group I: oxygen tension 136 +/- 2 mm Hg; pulmonary vascular resistance 120 +/- 3 x 10(3) dyne.sec/cm5; peak airway pressure 13 +/- 1 mm Hg and wet/dry weight ratio 3.6 +/- 0.3; p < 0.001 all parameters except pulmonary vascular resistance: p < 0.05. In contrast, grafts undergoing controlled pressure reperfusion (group III) achieved function comparable with baseline values at 2 hours: oxygen tension 137 +/- 3 mm Hg; pulmonary vascular resistance 132 +/- 7 x 10(3) dyne. sec/cm5; peak airway pressure 13 +/- 1 mm Hg; wet/dry weight ratio 4.1 +/- 0.3 (p = Not significant). CONCLUSIONS: The pressure at which pulmonary grafts are initially reperfused appears to be critical to their subsequent integrity. A protocol of controlled reperfusion may reduce reperfusion injury and improve graft function in clinical practice.

Adenosine↗

Canine skeletal muscle ventricles: functional assessment using the pressure-volume plane.

In five dogs, skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle, and placed within the thoracic cavity. After a 3-week delay period, SMVs were electrically preconditioned with 2-Hz continuous stimulation for 6 weeks. At a second procedure, SMVs were connected to a mock-circulation system, and performance was evaluated according to pressure-volume relationships at three different SMV contraction rates (33, 54, and 97 per min) and three stimulation protocols (25, 43, and 85 Hz) under varying loading conditions. Under appropriate conditions of afterload, the end-diastolic pressure-volume relation of SMVs was comparable with that of the cardiac ventricles, although SMVs were less compliant. At higher burst stimulation frequencies, SMV compliance was increased. Compliance was not affected by varying the rate of SMV contraction. End-systolic elastance, a reflection of contractility, appeared to be constant for each SMV, in contrast to cardiac ventricles, and was not influenced by changes in burst stimulation frequency or contraction rate. In this study, SMVs were capable of a level of stroke work 180% of that of the native right ventricle (RV) at rest (0.397 +/- 0.047 x 10(6) ergs) and 37% of that of the left ventricle (LV) at rest (0.298 +/- 0.61 x 10(6) ergs), at 33 contractions per minute (CPM), 25-Hz burst frequency, and physiological preload, but this level could not be sustained at higher contraction rates. Nevertheless, power output (SMV stroke work x contraction rate) was maximal at 97 CPM. These findings demonstrate important function differences between pumping chambers constructed from conditioned skeletal muscle, and those composed of cardiac muscle, which must be considered when using skeletal muscle ventricles for cardiac support or replacement.

Animals↗

Lung graft preservation. Comparison of phosphate-buffered sucrose, modified EuroCollins, and University of Wisconsin solutions.

Phosphate-buffered sucrose (PBS) has been shown to be highly effective for renal graft storage. It may, therefore, be useful for lung graft storage. Recent studies have suggested a possible role for University of Wisconsin (UW) solution in lung preservation. The object of this study was to evaluate these two solutions in comparison with EuroCollins (EC) solution for lung graft preservation in an isolated rat lung model. Lungs were stored for 6 hr at 4 degrees C after a single pulmonary artery flush with either PBS with prostacyclin (n = 10), EC with prostacyclin (n = 5), or UW (n = 5) solution. Reperfusion of the isolated lung was carried out for 1 hr using a venovenous extracorporeal circulation from a ventilated support rat. The support animals and isolated lungs were ventilated with room air. Control values were obtained from lungs reperfused immediately after harvesting (n = 5). At 1 hr, PBS provided a similar level of protection to EC: pO2, 45 +/- 10 mmHg and 54 +/- 6 mmHg; graft blood flow, 4.1 +/- 1.2 ml/min and 3.5 +/- 0.42 ml/min; peak airway pressure, 32 +/- 2.5 mmHg and 36 +/- 3.6 mmHg; weight gain, 4.1 +/- 0.6 g and 4.2 +/- 0.6 g, respectively (P = NS). However, the UW group provided superior function, which was similar to the control group: pO2, 128 +/- 2.7 mmHg and 126 +/- 5 mmHg; graft blood flow, 9.9 +/- 0.4 ml/min and 10.2 +/- 0.8 ml/min; peak airway pressure, 17.6 +/- 0.4 mmHg and 16.5 +/- 0.6 mmHg; weight gain, 0.12 +/- 0.1 g and 0.19 +/- 0.13 g, respectively (P = NS). UW was superior in all parameters to PBS and EC (P < 0.001). This suggests that the renal solutions PBS and EC are inappropriate for lung graft preservation, and that the requirements of the lung during hypothermic storage differ from those of the kidney.

Adenosine↗

Cardiomyoplasty: probable mechanism of effectiveness using the pressure-volume relationship.

The mechanism of effectiveness of cardiomyoplasty was evaluated in the setting of chronic left ventricular dysfunction in terms of the pressure-volume relationship. The distal branches of the left coronary artery were ligated in 12 sheep. Seven sheep died and the 5 survivors underwent cardiomyoplasty using a left latissimus dorsi graft 10 to 12 weeks later. These muscle grafts were then electrically conditioned for 2 months. The systemic pressure and cardiac output were not different between the postinfarction and postcardiomyoplasty period with the pacemaker off or on. However, the pressure-volume loops were altered by cardiomyoplasty in all 5 animals. Emax, which is an index of ventricular contractility, increased after cardiomyoplasty from 2.66 +/- 0.92 to 4.59 +/- 1.73 mm Hg/mL (mean +/- the standard deviation; p < 0.05), but did not change between the pacemaker off and on situations. The pressure-volume area, which strongly correlates with myocardial oxygen consumption, decreased after cardiomyoplasty (1,932 +/- 615 mm Hg.mL), compared with before cardiomyoplasty (3,776 +/- 1,201 mm Hg.mL) (p < 0.05), but did not change between pacemaker off and on. The probable mechanism responsible for the effectiveness of cardiomyoplasty is an "active" support or constraint of the damaged myocardium by the latissimus dorsi and the prevention of further ventricular dilation. This suggests that left ventricular systolic function can be augmented by cardiomyoplasty, but that it is a secondary mechanism of action.

Animals↗

Functional evaluation of intrathoracic versus extrathoracic skeletal muscle ventricles.

Skeletal muscle ventricles (SMVs) were constructed from the latissimus dorsi muscle in 10 dogs. In Group I (n = 5), SMVs were left in an extrathoracic position on the chest wall. In Group II (n = 5), SMVs were placed within the chest cavity. After a 3- to 4-week vascular delay period, SMVs were electrically preconditioned with 2 Hz continuous stimulation for 6 weeks. At a second procedure, SMVs were connected to a mock circulation system, and function was evaluated under differing conditions of preload and afterload. SMVs in Group II were significantly more compliant, as demonstrated by the end diastolic pressure volume relationship, than those in Group I (P < 0.01). SMVs in Group II were also capable of generating greater stroke work than those in Group I (P < 0.05). SMVs in Group II were also capable of greater stroke work than those in Group I at physiologic preloads (P < 0.05). These findings suggest that SMVs placed in an intrathoracic position exhibit better diastolic and systolic function.

Animals↗

Double cardiomyoplasty: acute versus chronic results.

We previously found that double cardiomyoplasty using both acutely raised, unconditioned latissimus dorsi muscles increased cardiac output by 9.6% (1,547 +/- 154 versus 1,695 +/- 166 mL/min), stroke volume by 18.2% (12.1 +/- 0.6 versus 14.3 +/- 0.7 mL), peak left ventricular pressure by 18.4% (98 +/- 3 versus 116 +/- 5 mm Hg), and peak right ventricular pressure by 62.5% (24 +/- 2 versus 39 +/- 4 mm Hg) (p < 0.05 for all differences). In this study 10 dogs underwent double cardiomyoplasty: 3 died perioperatively, and 7 underwent 8 weeks of muscle conditioning. After the conditioning period, the muscle flaps did not contract in 2 of the 7 dogs. Hemodynamics were measured in the remaining 5 dogs. Using fatigue-resistant muscle, cardiac output decreased by 3.7% (1,279 +/- 262 versus 1,233 +/- 274 mL/min), stroke volume decreased by 9.0% (9.5 +/- 1.2 versus 8.8 +/- 1.2 mL), and peak left ventricular pressure increased by 10.6% (82.1 +/- 6.5 versus 90.8 +/- 3.2 mm Hg), but not significantly. Peak right ventricular pressure increased significantly by 31.3% (24.3 +/- 2.1 versus 31.9 +/- 3.6 mm Hg; p < 0.05). Hemodynamic effects of individual left or right muscle contractions versus bilateral muscle stimulation were not significantly different except for a greater percentage increase in peak right ventricular pressure (right, 24.9 +/- 2.1 mm Hg unstimulated versus 28.0 +/- 2.1 stimulated; left, 26.3 +/- 0.9 mm Hg unstimulated versus 30.7 +/- 2.4 mm Hg stimulated; bilateral, 24.3 +/- 2.1 mm Hg unstimulated versus 31.9 +/- 3.4 mm Hg stimulated; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anaesthesia for cardiomyoplasty.

Cardiomyoplasty is a new surgical procedure for the treatment of severe heart failure, but early mortality has been high in the preliminary experience of many centres. This report describes the anaesthetic techniques used for the first two successful cases to be performed in the UK.

Anesthesia, General↗