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Biomedical subjects

G J Wilson

Publications and source records attributed to G J Wilson.

At least 127 records · Page 7Linked to original sources
PubMed1988

Inadequate myocardial protection with cold cardioplegic arrest during repair of tetralogy of Fallot.

Postoperative low cardiac output is the most common cause of death in patients undergoing elective repair of tetralogy of Fallot. The incidence is much higher than in elective adult bypass operations for coronary artery disease. To explain this difference, we investigated 16 children having elective repair of tetralogy (mean age 6.3 years). Myocardial biopsy specimens obtained during bypass before arrest, at the end of cold arrest by blood cardioplegia, and after 30 minutes of reperfusion were studied for adenosine triphosphate and lactate levels. Myocardium was submitted for microscopic study shortly after the onset of ischemia. The operation was successful in reducing right ventricular-pulmonary artery gradients from 82 +/- 28 to 9 +/- 1 mm Hg, yet seven patients required significant inotropic support (dopamine, greater than 5 micrograms/kg/min) for more than 24 hours and 12 patients needed prolonged use of digoxin and diuretics for right ventricular failure. Tissue levels of adenosine triphosphate and lactate in the tetralogy groups were compared with those in 20 adults with coronary artery disease having similar myocardial protection techniques. Adenosine triphosphate levels in the tetralogy group decreased during cross-clamping (41 +/- 8 minutes) from 24 +/- 3 to 16 +/- 2 mmol/kg dry weight (mean +/- 1 standard error), with a marked further drop after reperfusion to 9 +/- 2 mmol/kg (p less than 0.01). Adenosine triphosphate levels in the group with coronary disease also decreased from 20 +/- 1 to 16 +/- 1 mmol/kg after a longer cross-clamp time (70 +/- 17 minutes) but remained at 15 +/- 2 mmol/kg after reperfusion. Tissue lactate levels in the tetralogy group rose markedly during ischemia and remained elevated after reperfusion. In contrast, lactate levels in the group with coronary disease rose moderately during ischemia and returned to normal early on reperfusion. Microscopic study revealed focal myocyte necrosis in tetralogy of Fallot. Our findings, which demonstrate inadequate myocardial protection of patients with tetralogy during repair, with depression of adenosine triphosphate and increased lactate during ischemia and reperfusion, suggest a defect in oxidative metabolism. The drop in adenosine triphosphate after reperfusion in the patients with tetralogy implicates reperfusion injury as a mechanism of myocardial damage.

Adenosine Triphosphate↗
PubMed1988

Relationship between cerebrospinal fluid dynamics and reversible spinal cord ischemia during experimental thoracic aortic occlusion.

This study was designed to assess the effects of hemodynamic changes and cerebrospinal fluid dynamics on spinal cord function during experimental thoracic aortic occlusion. We investigated the effects of dopamine, sodium nitroprusside, and sodium thiopental in this model. Proximal and distal aortic pressures and cerebrospinal fluid pressure were measured during occlusion in 12 adult mongrel dogs under control conditions and during drug interventions. Spinal cord function was assessed by spinal somatosensory evoked potentials recorded during 3-minute intervals of reversible spinal cord ischemia. By multiple regression analysis, the degree of spinal cord ischemia was positively related to the cerebrospinal fluid pressure (p = 0.0092) and negatively related to the percent change in cerebrospinal fluid pressure (p = 0.028); there were no significant drug effects on cerebrospinal fluid pressure or on the degree of spinal cord ischemia. This study indicates that cerebrospinal fluid pressure is an important factor in determining the degree of spinal cord ischemia during aortic occlusion and suggests that measures to reduce cerebrospinal fluid pressure will mitigate the degree of spinal cord ischemia.

Animals↗
PubMed1988

The porous metal-surfaced heart valve. Long-term study without long-term anticoagulation in mitral position in goats.

On review, all thromboembolic complications in mechanical heart valves start from a thrombus lining that covers the suture ring. The thrombus organizes to a fibrous white sheet over the suture ring, which then can protrude out over the polished surface of the valve ring flange. Pieces of the thrombus can be knocked off by the disc and cause emboli. To diminish thromboembolic complications, one must either prevent this thrombus from protruding into the groove between the suture ring and the valve flange or allow the thrombus to be organized as a thin covering with endothelium-like cells as a continuation from the suture ring over the valve flange. This type of covering was obtained during a short period of anticoagulation by applying a microporous surface to the Björk-Shiley Monostrut mitral valve. These valves were implanted in one set of goats and the conventional Björk-Shiley Monostrut mitral valve, with a polished surface, in another set of goats (control group). The two groups were then compared with regard to the incidence of thromboembolic complications encountered during 1 year's follow-up without anticoagulation. The goats were put to death and examination revealed the following observations: In the control group, (1) a varying amount of thrombus formation was found in the groove between the suture ring and the flange in all nine goats and (2) thrombus formation did not start on the polished struts or discs in any of the nine goats. In the group with the microporous Monostrut mitral valve, 19 animals were put to death and examined: (1) The endothelialized covering over the suture ring, thinner when carbon coated, continued over the microporous flange, tapering off in the center of the orifice in all 19 valves on the ventricular side and in 14 of the 19 valves on the atrial side; (2) the center of the orifice and the struts were never completely covered by endothelialized tissue because of high flow; (3) there was an increased incidence of small thrombus formation on the disc-contacting microporous surface of both inflow and outflow struts. Therefore these surfaces should not be coated but left polished.

Animals↗
PubMed1988

The "border zone" in myocardial infarction. An ultrastructural study in the dog using an electron-dense blood flow marker.

There is controversy over the existence of a lateral "border zone" of intermediately injured tissue in the developing myocardial infarct (MI). The authors attempted an ultrastructural demonstration of this zone in serial subepicardial biopsies from developing MIs in dogs subjected to 90 minutes, 6 hours, or 24 hours of left anterior descending coronary artery ligation (4 dogs per group). After ligation, 400,000 units of horseradish peroxidase was infused through the left atrial appendage as a blood flow marker, to allow distinction of perfused and ischemic myocytes under electron microscopy. Evans blue stain was infused in the same way for gross guidance in harvesting biopsies across the lateral margins of the ischemic region. Interdigitation of perfused and ischemic tissue was observed over a lateral margin 6 mm wide, which caused admixture of perfused and ischemic myocytes in biopsies from this region. Ultrastructural ischemic injury was graded on a five-level qualitative scale (normal, mild, moderate, severe, lethal). Perfused myocytes from control and border sites were equivalently well preserved (79% normal, 21% mild injury, n = 353). Ischemic myocyte injury increased with duration of ischemia. At 90 minutes, 65% of ischemic myocytes had mild injury, 35% moderate (n = 138); at 6 hours, 17% of ischemic myocytes had moderate injury, 81% severe, 2% lethal (n = 115); at 24 hr, 100% of ischemic myocytes had lethal injury (n = 148). Severity of ischemic myocyte injury did not vary from the lateral border to the center of the ischemic region: there was no lateral "border zone." However, if myocytes were not separated into perfused and ischemic subpopulations before statistical comparison of biopsy site to severity of injury, false evidence of a "border zone" was obtained.

Animals↗
PubMed1987

Technique and postoperative management for successful cardiopulmonary bypass and open-heart surgery in dogs.

Twenty-six healthy mixed-breed dogs (25 to 35 kg) underwent hypothermic (27 C) cardiopulmonary bypass. The heart was arrested with cold (4 C) cardioplegic solution, and left ventriculostomy performed. Postoperative mortality was 11.5% (3/26). Two deaths were attributable to ventricular fibrillation the night after surgery, and one death 2 weeks later was the result of pulmonary embolization. All other dogs recovered promptly and were well at follow-up evaluation 6 weeks later. The most important considerations were (1) the surgical approach, ie, combining left lateral thoracotomy with cannulation of the right atrium and left femoral artery for cardiopulmonary bypass (CPB) (avoiding median sternotomy and aortic arch perfusion), (2) the adherence to strict criteria for CPB perfusion, consisting of blood flow of at least 2.2 L/m2/min, PCV no less than 25%, gas flow through the oxygenator (97% O2, 3% CO2) of at least 3.5 L/min, maintenance of a mean arterial blood pressure greater than 60 mm of Hg, and heparinization to maintain activated clotting time over 480 seconds, (3) the use of dipyridamole infusion to preserve platelets during CPB, resulting in decreased postoperative blood loss and (4) the monitoring of cardiac, respiratory, renal, and neurologic functions before, during, and after the operation, with particular emphasis on fluid balance and electrolytes. We concluded that a high success rate is possible for open-heart surgery in the dog requiring cardiopulmonary bypass, but only through meticulous surgical technique and the combined application of many monitoring techniques, with timely intervention to correct serious departures from homeostasis.

Animals↗
PubMed1987

The effect of low-flow cardiopulmonary bypass on cerebral function: an experimental and clinical study.

Systemic flow rates (Q) during nonpulsatile hypothermic cardiopulmonary bypass (CPB) that are consistent with preservation of cerebral function have not to our knowledge been objectively defined. The effect of a sequential reduction in flow rates on cerebral cortical metabolism and function was evaluated in 6 mongrel dogs during hypothermic (25 degrees C) CPB. Cerebral function was assessed using somatosensory cortical evoked potentials (SSEP); cerebral metabolism was assessed by adenosine triphosphate (ATP) and lactate content of snap-frozen gray matter biopsies taken from the hemisphere contralateral to that monitored for SSEP. A progressive decline in ATP levels was observed during flow reduction with virtually complete depletion of ATP at 0.25 L min-1 m-2(p = .0003). The significant (p = .028) dependence of cortical ATP levels on perfusion pressure was no longer evident after adjusting for the effects of flow rate. Lactate levels increased during flow reduction (p = .028), especially at flow rates less than 0.5 L min-1 m-2. Somatosensory neural transmission remained intact until flow was reduced to 0.25 L min-1 m-2 in 5 animals and until total circulatory arrest in 1, at which time loss of the signal occurred. In addition, 5 patients were subjected to brief periods of low-flow CPB (Q = 1.0 L min-1 m-2) at 21 degrees to 25 degrees C. SSEPs remained intact during flow reduction, and postoperative neurologic evaluation was normal in all patients. We conclude that, in the absence of cerebral vascular disease, the flow rate threshold for incurring functional cerebral injury during hypothermic (25 degrees C) nonpulsatile CPB is less than 1.0 L min-1 m-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

Conjugated dienes in ischemic and reperfused myocardium: an in vivo chemical signature of oxygen free radical mediated injury.

Free radical reactions have been suggested to be important events in the mechanism of myocardial injury during ischemia and reperfusion. Most of the in vivo evidence implicating free radical mediated events in the etiology of myocardial injury has been based on intervention studies which document the efficacy of oxygen free radical scavengers in improving function or tissue salvage. We have assayed free fatty acid oxidation products (hydroxy conjugated dienes) derived from myocardial phospholipid as chemical markers of oxidative injury. Biopsies, harvested from canine myocardium subjected to cardiopulmonary bypass with no aortic crossclamp (control), from pre-ischemic, end ischemic (at the end of 45 min of global normothermic ischemia induced by aortic crossclamp) and at 5, 10, 15, 30 and 60 mins of reperfusion were analyzed for hydroxy conjugated dienes using HPLC with structural confirmation by GC-MS. All biopsies were taken from non-necrotic myocardium as indicated by gross tetrazolium staining of myocardial cross sections. Trace levels of hydroxy conjugated dienes could be detected in the preischemic biopsies or control biopsies harvested from hearts subjected to cardiopulmonary bypass with no ischemia. At the end of 45 min ischemia, however, a significant increase in 18:2 and 20:4 hydroxy isomers was detected and confirmed by GC-MS (P less than 0.05 vs. control). After 5 mins of reperfusion a further significant increase in hydroxy conjugated dienes was noted with 18:2, 20:4 and 22:6 isomers being identified (P less than 0.01 vs. end ischemia). By 30 min of reperfusion the concentration of phospholipid oxidation products had returned to pre-ischemic levels. This study presents the first chemically rigorous in vivo evidence for the formation of products of phospholipid oxidation (hydroxy conjugated dienes) during myocardial ischemia and reperfusion and supports the concept of oxygen free radical mediated lipid peroxidation. This study emphasizes the formation of phospholipid oxidation products during ischemia and particularly during the early phase of reperfusion and illustrates the transient nature of these products in myocardial phospholipid.

Animals↗
PubMed1987

Impaired left ventricular postischemic function and metabolism in chronic right ventricular hypertrophy.

Chronic right ventricular hypertrophy (RVH) has been shown to produce changes in left ventricular diastolic properties but minimal effects on left ventricular systolic function. We studied the effects of chronic pressure overload RVH on left ventricular systolic function before and after reversible hypothermic global ischemia. RVH was induced by pulmonary artery banding (PAB) in newborn piglets (5 to 7 days). At 2 months of age the PAB group (n = 6) and a control group (n = 8) were subjected to cardiac arrest on cardiopulmonary bypass with cold crystalloid cardioplegia (10 degrees C) for 2 hr and were reperfused for 1 hr. Left ventricular function was assessed by a conductance catheter in the left ventricle measuring the end-systolic pressure-volume relationship (Emax). Preischemic and postischemic Emax were the same in the control group (4.1 +/- 0.4 mm Hg/ml before vs 4.1 +/- 0.4 mm Hg/ml after ischemia), but significantly different in the PAB group (4.7 +/- 0.5 mm Hg/ml before vs 2.97 +/- 0.7 mm Hg/ml after ischemia, p less than .05). There also was a marked drop in ATP and phosphocreatine (CP) content in the PAB group during ischemia (ATP, 20 +/- 2 mmol/kg dry wt before vs 10 +/- 2 mmol/kg dry wt after ischemia, p less than .05; PC, 26 +/- 3 mmol/kg dry wt before vs 11 +/- 1 mmol/kg dry wt after ischemia, p less than .05). In the control group there was no change in ATP content and, although CP did drop by end-ischemia, there was complete recovery by 1 hr of reperfusion but minimal CP recovery in the PAB group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1987

Evidence of myocardial free radical injury during elective repair of tetralogy of Fallot.

Evidence of human myocardial oxygen-mediated free radical injury (OFRI) during cardiovascular repair is lacking. We studied six cyanotic children (ages 3.5 to 5.5 years) during elective repair of tetralogy of Fallot. Right ventricular biopsy specimens, obtained on bypass just before aortic cross-clamping, at the end of 40 +/- 8 min (mean +/- SD) cold arrest with blood cardioplegia, and during reperfusion, were analyzed for hydroxy conjugated dienes, a chemical signature of free radical injury. Structural confirmation of the dienes was done by mass spectroscopy. Conjugated dienes were detected before ischemia on bypass, at end-ischemia, and during reperfusion. The products identified are 9 and 13 OH isomers of linoleic acid and 5, 8, 9, 11, and 15 OH isomers of arachidonic acid. Microscopic examination of right ventricular biopsy specimens obtained on bypass just after cross-clamping showed focal myocyte necrosis. The hydroxy conjugated diene levels in control canine hearts subjected to 105 min of cardiopulmonary bypass without aortic cross-clamping were not detectable. Our results support the occurrence of oxygen-mediated free radical injury during elective repair of tetralogy of Fallot. The presence of conjugated dienes before aortic cross-clamping suggests oxygen toxicity with reoxygenation from cardiopulmonary bypass.

Animals↗
PubMed1987

Comparison of left ventricular assist and intra-aortic balloon counterpulsation during early reperfusion after ischemic arrest of the heart.

In most centers, intra-aortic balloon counterpulsation and inotrope infusion are used for patients who require support to be weaned from cardiopulmonary bypass at the end of a cardiac surgical procedure. Where available, early institution of a left ventricular assist device is an alternative with possible advantages. In a canine model of left ventricular failure caused by 45 minutes of normothermic ischemic arrest, these two methods of support were instituted after an initial 30-minute reperfusion period. Both methods provided adequate support of the circulation (cardiac output greater than 2 L/min and mean arterial pressure greater than 50 mm Hg). After only 3 hours, however, significant differences were seen between the two groups. When the hearts were examined histologically, dogs in the group with intra-aortic balloon counterpulsation and inotrope infusion had significantly more necrosis than those in the group with a left ventricular assist device, 7.7% +/- 5.0% (mean +/- standard deviation) versus 2.0% +/- 1.3%. Decreases in compliance and systolic function were significantly greater in the group with intra-aortic balloon counterpulsation and inotrope infusion when compared with those supported with a left ventricular assist device. These findings suggest that even when support with intra-aortic balloon counterpulsation and inotrope infusion resulted in satisfactory hemodynamics, early institution of a left ventricular assist device was significantly more effective in preserving myocardial structure and function.

Animals↗
PubMed1987

Age-related differences in the response to myocardial ischemic stress.

Clinical experience indicates that the risk of reparative cardiac operations is increased in the neonatal period relative to that in older infants and children. Age-related differences in the susceptibility to myocardial ischemic dysfunction were evaluated by comparison of left ventricular function and metabolism in neonatal (mean age = 7 days) and weanling (mean age = 96 days) piglets. Six animals in each group supported on cardiopulmonary bypass were subjected to (1) 120 minutes of hypothermic crystalloid cardioplegic arrest (CP-120) and (2) 15 minutes of normothermic ischemic arrest (NA-15) after a 60 minute interval of reperfusion. Left ventricular systolic and diastolic function was measured after each intervention via endocardially implanted ultrasonic dimension crystals in a septolateral minor-axis position. In both groups, systolic dysfunction was evidenced by an increase in the dimension-axis intercept (p = 0.001), but not the slope of the end-systolic pressure-dimension relation. Left ventricular end-diastolic stiffness, expressed as left ventricular end-diastolic pressure versus Lagrangian strain, increased to a similar degree in both groups (p = 0.001). Adenosine triphosphate levels declined significantly (p = 0.001) in both groups in response to the ischemic interventions with no evident intergroup differences. Lactate levels increased significantly during the course of the experiment (p = 0.04); however, the increases were greater (p = 0.009) at all intervals in the neonatal group. This study demonstrates age-related metabolic differences in response to ischemia consistent with a greater dependence on glycolysis in neonatal myocardia. However, the fact that discriminating age-related differences in left ventricular function were not evident suggests that factors other than young age per se account for the increased surgical mortality in the neonatal period.

Adenosine Triphosphate↗
PubMed1986

Cerebral complications following balloon angioplasty of coarctation of the aorta.

A 10-month-old male child underwent balloon angioplasty for a recurrent coarctation of the aorta. Postprocedural hemorrhagic cerebral infarction led to the child's death. At necropsy, hypoplasia of the left posterior communicating artery of the circle of Willis was found. The implications of such variations in cerebral blood flow circulation on the angioplasty technique are presented and discussed.

Angioplasty, Balloon↗
PubMed1986

Anisotropic tensile viscoelastic properties of vascular graft materials tested at low strain rates.

Mechanical matching of vascular grafts and host vessels has been suggested to be important in determining graft patency rates. In this context, we have examined the anisotropic viscoelastic properties of natural vessels and some synthetic replacements using low strain rate tensile testing of circumferential and longitudinal strips. The canine iliac artery and iliac vein were compared with 6 mm diameter woven and knitted Dacron grafts, expanded polytetrafluoroethylene (PTFE) grafts, and helically constructed prototype polyurethane grafts at wrap angles of 45, 60 and 75 degrees. A thick-walled pressure vessel analysis was used to approximate physiological stress levels, and SEM was used to correlate anisotropic properties with graft wall structure.

Animals↗
PubMed1986

Exogenous substrate preference of the post-ischaemic myocardium.

Myocardial exogenous substrate preference was studied under conditions of increased plasma lactate concentration before and after a severe (halving of tissue ATP concentration, sixfold increase in tissue lactate concentration) but reversible (less than 1% necrosis on reperfusion) global ischaemic stress produced by continuous hypothermic electromechanical arrest of the heart of four hours' duration by aortic cross clamping and multidose potassium cardioplegia. Fatty acid oxidation was studied using 1-14C-palmitate under steady state conditions and under similar isovolumic fixed pressure conditions with the heart at a constant rate using a left ventricular intracavitary balloon. Exogenous free fatty acid oxidation during the pre-ischaemic period with an increased lactate concentration (3.9-5.8 mmol . litre-1) was 0.62(0.21) mumol . min-1 X 100 g-1 (mean (SEM)). This represented a mean of 32% of the total carbon dioxide produced in contrast to a post-ischaemia free fatty oxidation rate of 2.67(0.87) mumol . min-1 X 100 g-1, in the presence of even further increased plasma lactate concentrations (8.47-11.17 mmol . litre-1), representing a mean of 82% of the total carbon dioxide output. These data suggest that the substrate preference of the myocardium, under conditions of increased plasma lactate concentration, shifts to greater oxidation of exogenous free fatty acids after ischaemic stress.

Adenosine Triphosphate↗
PubMed1986

Metabolic response of skeletal muscle to ischemia.

To evaluate the temporal relationship and potential correlation between intramuscular phosphagen levels, lipid oxidation, and extent of muscle injury, a canine gracilis muscle model was used to study the consequences of a global ischemic episode for up to 7 h duration with reperfusion for 4 h. In this model the contralateral gracilis muscle was prepared identically to the test side but was not subjected to ischemia and thus served as a control. Blood flow, oxygen consumption, and lactate and glycerol release were measured before and after 2- and 7-h ischemic stress periods. The intramuscular metabolites, glycogen, lactate, phosphocreatine, and ATP, as well as free fatty acid conjugated dienes, were measured before, during, and after the ischemic insult. A 2-h ischemic insult resulted in minimal ultrastructural damage and complete regeneration of intramuscular phosphagens and glycogen on reperfusion with complete normalization of lipid oxidation products. In contrast, a 7-h ischemic insult resulted in profound injury at the ultrastructural level with an inability to restore intramuscular phosphagens and glycogen on reperfusion. This severe muscle injury correlated with a 2.5-fold increase in lipid oxidation products (free fatty acid conjugated dienes) and a decline in ATP levels below 5 mumol/g dry wt on reperfusion. Our results emphasize the prolonged glycolytic activity of skeletal muscle during global ischemia and document the increased production of oxygen free radical-mediated lipid oxidation products in irreversibly injured muscle.

Adenosine Triphosphate↗
PubMed1986

ACTH-producing microadenoma of the pituitary in a young female infant with Cushing's disease: report of a case including immunocytologic and ultrastructural studies.

A female infant, younger than any other case in the literature, with ACTH-producing microadenoma of the pituitary is reported. She had full-blown symptoms and signs as well as laboratory evidence of Cushing's disease. The tumor was investigated by histology, immunocytology (avidin-biotin-peroxidase complex technique), and electron microscopy. The possibility that the tumor was derived from the fetal intermediate lobe is discussed.

Adenoma↗
PubMed1986

Endocardial excision versus encircling endocardial ventriculotomy. A comparison of effects on ventricular structure and function.

Although endocardial excision and encircling endocardial ventriculotomy are being performed in patients with extensive triple-vessel disease and compromised ventricular function, long-term effects of the operative intervention on structure and function of the left ventricle have not been determined. These procedures were performed in healthy dogs in three groups: control (ventriculotomy alone), endocardial excision, and encircling endocardial ventriculotomy (five dogs per group). Six weeks later, through a left thoracotomy, an arterial line, left atrial line, and Swan-Ganz catheter were inserted. Cardiac output measurements permitted calculation of left ventricular stroke work index, and gated nuclear ventriculograms permitted calculation of left ventricular volume indices. Myocardial performance (stroke work index/end-diastolic volume index relation), systolic elastance (systolic blood pressure/end-systolic volume index relation) and diastolic pressure-volume relationship (left atrial pressure/end-diastolic volume index relation) were determined from volume loading studies. In the endocardial excision group, the left atrial pressures were increased at similar end-diastolic volumes (p less than 0.05 by performance and systolic elastance were similar in the three groups. On completion of hemodynamic studies, the hearts were excised. Gross and light microscopic examination showed that the inner layer of myocardium was scarred in the area of intervention after both endocardial excision and encircling endocardial ventriculotomy. In neither group was there significant morphologic change elsewhere in the myocardium. Both endocardial excision and encircling endocardial ventriculotomy have little effect on long-term structure and function when performed in healthy canine hearts.

Animals↗