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Biomedical subjects

T J Gardner

Publications and source records attributed to T J Gardner.

At least 55 records · Page 3Linked to original sources
PubMed1996

A1 adenosine receptor antagonists block ischemia-reperfusion injury of the heart.

BACKGROUND: It has been reported that A1 adenosine receptor antagonists are highly effective for the prevention and early treatment of ischemia-reperfusion injury of isolated perfused cat lung, which suggests that activation of A1 adenosine receptors is important in ischemia-reperfusion injury of the lung. In addition, preconditioning ischemia reduces ischemia-reperfusion injury of the lung and heart. Moreover, activation of A1 adenosine receptors by adenosine and selective A1 adenosine receptor agonists mimics the protective effects of preconditioning ischemia in the heart. It has been reported that prior treatment with selective A1 adenosine receptor agonists results in a rapid uncoupling of A1 adenosine receptors from signal transduction mechanisms. In the heart, these effects of A1 adenosine receptor agonists have not been reported. However, if prior treatment of ischemia of the heart with adenosine or A1 adenosine receptor agonists results in uncoupling of A1 adenosine receptors from signal transduction mechanisms that produce injury after prolonged ischemia and reperfusion, A1 adenosine receptor antagonists should provide a protective effect similar to these treatments for ischemia-reperfusion injury of the heart. Therefore, it was the purpose of these experiments to investigate the effect of selective A1 adenosine receptor antagonists on ischemia-reperfusion injury of the heart. METHODS AND RESULTS: With the use of a regional infarct model in open-chest cats, the left anterior descending artery or first diagonal branch was occluded for 1 hour followed by 2 hours of reperfusion. Infarct size (area of necrosis/area at risk; AN/AR) was estimated with the use of nitroblue tetrazolium staining. The selective A1 adenosine receptor antagonists xanthine amine congener (XAC; 0.1 mg.kg-1.h-1), bamifylline (BAM; 10 mg.kg-1.h-1), 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 micrograms.kg-1.min-1) administered as continous intravenous infusions for 1 hour before ischemia [DPCPX (I)], or DPCPX 30 micrograms.kg-1.min-1 administered intravenously during 30 minutes of ischemia and 30 minutes of reperfusion [DPCPX (I/R)] significantly (P < .05) reduced AN/AR from 52.2 +/- 3.8% (control, n = 5) to 23.4 +/- 6.6% (XAC, n = 5), 34.9 +/- 3.6% (BAM, n = 5), 15.9 +/- 2.9% [DPCPX(I), n = 5], or 13 +/- 3.2% [DPCPX (I/R), n = 5]. CONCLUSIONS: A1 adenosine receptor antagonists significantly reduce ischemia-reperfusion injury of the heart. A1 adenosine receptor antagonists may be useful for the prevention or early treatment of ischemia-reperfusion injury of the heart after coronary artery bypass graft surgery or cardiac transplant surgery and during or after angioplasty or thrombolytic therapy of the heart.

Animals↗
PubMed1996

Triiodothyronine optimizes sheep ventriculoarterial coupling for work efficiency.

BACKGROUND: Triiodothyronine (T3) administration after cardiopulmonary bypass has been shown to significantly improve cardiac performance. The present study was undertaken to elucidate the effects of T3, when administered as an intravenous bolus, on both cardiac energetics and stroke work-oxygen utilization (EW/LVVO2) efficiency. METHODS: In both unstressed and stressed hearts, energetics were evaluated at baseline and 2 hours after intervention in an in vivo sheep preparation. In the first group (n = 5) sheep received saline vehicle. In the second group (n = 9) sheep received an intravenous bolus of 1.2 micrograms/kg of T3. In the third group (n = 7) sheep received a 2-hour intravenous infusion of dobutamine at a rate of 5 micrograms/kg/min. RESULTS: In the unstressed heart, T3 improved cardiac function at no cost in oxygen consumption by decreasing afterload and hence improved EW/LVVO2 efficiency. In contrast, dobutamine improved unstressed cardiac function by increasing contractility at the cost of increased oxygen consumption and thus decreased EW/LVVO2 efficiency. Triiodothyronine optimized ventriculoarterial coupling for efficiency, but dobutamine optimized coupling for maximal work. In the stressed heart, T3 again improved EW/LVVO2 efficiency, but dobutamine had the opposite effect. CONCLUSIONS: The bolus administration of T3 improves unstressed cardiac performance through optimization of ventriculoarterial coupling for EW/LVVO2 efficiency, primarily through vasodilation. Triiodothyronine also increases efficiency in the stressed heart. This study supports the use of T3 in cardiac operations to improve cardiac performance with no cost in oxygen consumption characteristic of inotropic agents.

Animals↗
PubMed1996

Detection of stroke during cardiac operations with somatosensory evoked responses.

OBJECTIVES: The objectives of this study were to determine if monitoring of intraoperative somatosensory evoked potentials could be used to detect stroke during cardiac operations and to establish indicators of cerebral ischemia based on changes in these potentials. METHODS: Twenty-five patients undergoing cardiac operations underwent preoperative and postoperative neurologic examinations as well as intraoperative recording of somatosensory evoked potentials. Detailed analysis of the waveforms of these potentials was performed. RESULTS: Two of the 25 patients had intraoperative strokes. These patients and only these patients had changes in their somatosensory evoked potentials during the operation suggesting cerebral ischemia. The unilateral disappearance of the cortical somatosensory evoked potential waves correlated significantly with the clinical outcome of stroke (p < 0.004). Ischemic changes were detected in real time and were related to the removal of the aortic crossclamp in one patient and to the initiation of cardiopulmonary bypass in the other. CONCLUSIONS: Somatosensory evoked potentials can detect intraoperative stroke during cardiac operations. Acute, unilateral decreases in amplitude of the cortical potential are more useful than changes in latency in detecting intraoperative stroke.

Adult↗
PubMed1995

Reverse remodeling from cardiomyoplasty in human heart failure. External constraint versus active assist.

BACKGROUND: Cardiomyoplasty (CM) is a novel surgical therapy for dilated cardiomyopathy. In this procedure, the latissimus dorsi muscle is wrapped around the heart and chronically paced synchronously with ventricular systole. While studies have found symptomatic improvement from this therapy, the mechanisms by which CM confers benefit remain uncertain. This study sought to better define these mechanisms by means of serial pressure-volume relation analysis. METHODS AND RESULTS: Serial pressure-volume studies were performed by the conductance catheter method in three patients (total to date) with dilated cardiomyopathy (New York Heart Association class III) who underwent CM. Data were measured at baseline (before surgery) and at 6 and 12 months after CM. Chronic left ventricular (LV) systolic and diastolic changes induced by CM were evaluated with the stimulator in its stable pacing mode (every other beat) and after temporarily suspending pacing. CM-stimulated beats were compared with pacing-off beats to evaluate active systolic assist effects of CM. In each patient, CM resulted in a chronic lowering of cardiac end-diastolic volume and an increased ejection fraction. Most notably, the end-systolic pressure-volume relation shifted leftward, consistent with reversal of chronic chamber remodeling. In contrast, the diastolic pressure-volume relation was minimally altered, and the loops shifted down along the same baseline relation. These marked chronic changes in LV function measurable with CM stimulation off contrasted to only minor acute effects observed when the muscle wrap was activated. This suggests that the benefit of CM derived less from active systolic assist than from remodeling, perhaps because of an external elastic constraint. CONCLUSIONS: These data, while limited to a small number of patients, suggest that CM can reverse remodeling of the dilated failing heart. While systolic squeezing assist effects of CM may play a role in some patients, our study found that this was not required to achieve substantial benefits from the procedure. We speculate that CM may act more passively, like an elastic girdle around the heart, to help reverse chamber remodeling.

Adult↗
PubMed1995

Repair of coarctation of the aorta in neonates and infants: a thirty-year experience.

Between January 1962 and December 1991, 179 children less than 1 year of age underwent repair of coarctation of the aorta. Group I (1962 to 1971) consisted of 19 patients, group II (1972 to 1981) of 57 patients, group III (1982 to 1991) of 103 patients. Neonates (< 30 days old) made up 60% of group I, 57% of group II, and 70% of group III. The proportion of infants with associated complex cardiac abnormalities was 7% in group I, 25% in group II, and 39% in group III. Techniques of repair included resection with end-to-end anastomosis (n = 65), subclavian flap repair (n = 85), patch aortoplasty (n = 18), and other procedures (n = 11). The early mortality (< 30 days) was lowest in group III (group I, 21%; group II, 21%; and group III, 7%; p < 0.05), but the late mortality was similar in all groups (group I, 11%; group II, 13%; and group III, 15%). The overall actuarial survival was 57.7% +/- 0.15% at 27.1 years in group I, 65.7% +/- 0.07% at 19.7 years in group II, and 77.5% +/- 0.04% at 9.3 years in group III (p = not significant). Twenty-five restenoses requiring intervention occurred in 23 patients, for an overall restenosis rate of 16.4%. The incidence of restenosis was 23% for the patients who underwent end-to-end anastomosis, 11% for those who underwent subclavian flap repair (p < 0.1), and 27% for those who underwent patch aortoplasty (p < 0.01). Balloon angioplasty was successful in relieving 11 of the 12 restenoses in groups II and III.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Multiple↗
PubMed1995

Retrograde cerebral and distal aortic perfusion during ascending and thoracoabdominal aortic operations.

BACKGROUND: Several alternative circulatory management techniques during thoracic aortic reconstruction have been implemented at this institution. This study was performed to assess whether retrograde cerebral perfusion during proximal aortic operations and distal aortic perfusion during thoracoabdominal aortic operations have improved outcomes. METHODS: A retrospective review of 156 patients undergoing elective and emergent operations of the thoracic aorta over the past 7 years was performed. Seventy-five patients underwent proximal aortic procedures: 22 with ascending aneurysms, 45 with type A dissections, and 8 with arch reconstructions. Eighty-one patients underwent descending thoracic or thoracoabdominal procedures: 26 with Crawford type I aneurysms, 18 with type II, 8 with type III, 8 with type IV, 11 with traumatic transections, and 10 with type B dissections. Outcomes measured were neurologic injury, renal failure, and mortality. RESULTS: For proximal aortic procedures, the stroke rate was 12% using cardiopulmonary bypass and 48% using hypothermic circulatory arrest. The addition of retrograde cerebral perfusion decreased the stroke rate to 0% (p < 0.01) and the mortality rate to 7.1% compared with 37% for hypothermic circulatory arrest (p < 0.05). For thoracic and thoracoabdominal aortic operations, straight cross-clamping resulted in a 27% rate of spinal cord injury and a 24% rate of renal failure, whereas the addition of distal aortic bypass resulted in a statistically significant reduction (p < 0.01) in neurologic injury to 7% and a notable, but not statistically significant, decrease in renal failure to 13%. Distal aortic bypass also reduced the mortality rate from 22% to 7% (p < 0.05). CONCLUSIONS: Retrograde cerebral perfusion decreases the stroke rate and mortality rate in proximal aortic operations and distal aortic perfusion decreases the rates of neurologic injury, renal failure, and mortality in thoracoabdominal aortic operations.

Aortic Dissection↗
PubMed1994

New method for mechanistic studies of cardiomyoplasty: three-dimensional MRI reconstructions.

The imaging modalities used to study the mechanism of cardiomyoplasty, such as echocardiography and radionuclide scintigraphy, are seriously limited by their two-dimensional format. Radiofrequency-pulse-tagged magnetic resonance imaging was used to generate three-dimensional reconstructions of the left ventricle throughout the cardiac cycle after cardiomyoplasty. In 2 dogs that had undergone conditioned, right anterior cardiomyoplasty, wrap stimulation with alternating heartbeats was found to produce marked translation of the left ventricle in the short-axis plane, rotation around the long axis, and displacement along the long axis with net long-axis compression; there was no augmentation of radial squeeze. The findings from this study suggest that any systolic augmentation produced by the right anterior wrap is due primarily to long-axis compression. Our study demonstrates a new, more accurate technique of assessing the mechanical effects of cardiomyoplasty in three dimensions, thus permitting a more rational optimization of wrap configurations, and emphasizes the perils of using standard two-dimensional imaging modalities in this setting of exaggerated three-dimensional motion.

Animals↗
PubMed1994

Oxygen radicals and myocardial stunning.

There is compelling, although indirect, evidence that oxygen free radicals, generated during ischemia as well as upon reperfusion and reoxygenation of the ischemic heart, contribute to the reversible ventricular dysfunction characterized as myocardial stunning. Evidence of cell membrane damage as well as depression of sarcoplasmic reticulum and mitochondrial function with resulting calcium overload of the cell may be a result of lipid peroxidation of the cell by free radical products. Radical scavenger enzymes have been shown to greatly reduce the appearance of mRNA of a stress response protein (heat shock protein 71) in a pig heart model of stunning. The potential role for the introduction of antioxidant enzymes or stress protein in the cell is presented as a possible strategy for attenuating free radical damage during postischemic reflow.

Animals↗
PubMed1993

Pressure-volume analysis of changes in cardiac function in chronic cardiomyoplasty.

Reports of clinical improvement in human studies of dynamic cardiomyoplasty lack support by consistent objective hemodynamic evidence. Animal studies have also yielded conflicting results, likely due to nonuniform models, particularly the use of unconditioned wraps, and to limitations in commonly used study modalities caused by exaggerated heart motion during wrap stimulation. Our purpose was to assess the primary functional properties of the heart wrapped by conditioned muscle using pressure-volume relation analysis based on conductance catheter volume data. Compared with the unstimulated state, 1:1 stimulation caused an increase in contractility and decreases in end-diastolic volume and stroke work. Assisted beats during 1:2 stimulation showed an increase in contractility and a decrease in end-diastolic volume. Unassisted beats (1:2) showed decreases in end-diastolic volume and stroke work. There was no augmentation of cardiac output or ejection fraction with stimulation (1:1 or 1:2). We conclude that in the nonfailing heart, increased contractility does not augment cardiac output, ejection fraction, and stroke work because of a simultaneous decrease in end-diastolic volume. These changes in contractility and end-diastolic volume may prove therapeutic for dilated cardiomyopathy.

Animals↗
PubMed1993

Leukocyte depletion in a neonatal model of cardiac surgery.

Neonatal cardiac surgical procedures continue to be associated with a considerable incidence of severe post-operative ventricular dysfunction. The role of neutrophils in mediating such injury has recently been proposed but remains controversial. The present study was undertaken to examine the potential benefits of leukocyte depletion for myocardial preservation using an in situ, in vivo porcine model of neonatal cardiac surgery. Sixteen 3- to 5-day-old piglets, 8 controls and 8 leukocyte-depleted animals (LD group), underwent 90 minutes of hypothermic ischemia. Mechanical leukocyte filtration during cardiopulmonary bypass reduced the granulocyte count in the initial reperfusate to 0.7% of controls. This was associated with a reduction in leukocyte sequestration in the coronary vascular bed (p < 0.005), a decrease in myocardial creatine kinase release (p < 0.02), and a reduction in coronary vascular resistance (p < 0.03). These changes in physiological response to ischemia were associated with improved postischemic recovery of left ventricular systolic function in LD animals (p < 0.05), although there was no significant improvement in diastolic function. Application of this technique in neonatal cardiac operations may improve myocardial protection and reduce the associated morbidity and mortality.

Animals↗
PubMed1993

Valvular disease in the elderly: influence on surgical results.

Aortic valve disease in the elderly is primarily calcific stenosis with preservation of left ventricular function. In contrast, mitral valve disease in the elderly often is ischemic in nature with damage occurring to both valve and myocardium. The present study was undertaken to compare results of aortic (AVR) and mitral valve replacement (MVR) in the elderly and to ascertain predictors of poor outcome. Because patients who had concomitant coronary artery bypass grafting (CABG) are included (51% for AVR, 55% for MVR), patients who had isolated CABG were used as a comparison group. Between January 1, 1984, and June 30, 1991, 1,386 patients aged 70 years and older underwent CABG (n = 1,043), AVR (n = 245), or MVR (n = 98). The operative mortality rates were 5.3% for AVR, 20.4% for MVR, and 5.8% for CABG. Late follow-up of patients undergoing operation in 1984 and 1985 was available for 98% (231/237). Overall survival was comparable for all three groups through the first 5 years of follow-up (AVR, 68% +/- 8%; MVR, 73% +/- 8%; CABG, 78% +/- 3%). After 5 years, survival for patients having AVR and MVR was less than that for those having CABG. Patient age, sex, New York Heart Association functional class, concomitant CABG, prosthetic valve type, native valve pathology, and preoperative catheterization data were examined as possible predictors of outcome by multivariate logistic regression.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Inhibition of neutrophil adhesion reduces myocardial infarct size.

Neutrophil accumulation and activation within the myocardium during ischemia and reperfusion has been shown to play a prominent role in the development of myocardial stunning and infarction. To determine if a simple inhibitor of neutrophil adhesion could reduce myocardial infarct size, we administered NPC 15669 (a new antiinflammatory agent that inhibits neutrophil adhesion) to 12 pigs (6 controls, 6 NPC-treated) in a porcine model of ischemia and reperfusion injury. Each animal received a continuous infusion of either NPC (10 mg/kg intravenous bolus followed by 6 mg.kg-1 x h-1 intravenous infusion) or an equal volume of normal saline solution during 1 hour of left anterior descending artery occlusion and 2 hours of reperfusion. There were no significant differences in the pre-ischemia, mid-ischemia, or postischemia rate-pressure product between control and experimental groups. The regions at risk were similar in both groups. However, the mean myocardial infarct size was reduced by 51% with administration of NPC 15669 (30.7% +/- 6.8%) compared with controls (62.3% +/- 5.4%; p < 0.01). These data indicate that NPC 15669, an inhibitor of neutrophil adhesion, substantially reduces myocardial infarct size after transient left anterior descending artery occlusion and that adhesion of the white cell to vascular endothelium may be an important element of the pathogenesis of myocardial infarction.

Animals↗
PubMed1993

Centrifugal ventricular assist device for support of the failing heart after cardiac surgery.

OBJECTIVE: To determine the morbidity and mortality associated with use of centrifugal ventricular assist devices for postcardiotomy cardiogenic shock and to determine factors that might influence outcome and thus, aid in patient selection. DESIGN: A retrospective study. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: During a 6-yr period, a total of 7,385 adult patients underwent cardiac operations requiring cardiopulmonary bypass. Myocardial protection consisted of single-dose cold crystalloid cardioplegia and continuous topical hypothermia by saline lavage. A total of 72 (1%) patients developed postcardiotomy cardiogenic shock. Of 72 patients, 28 met the institutional criteria and were placed on centrifugal ventricular assist devices. INTERVENTIONS: Twenty-eight adult patients with postcardiotomy cardiogenic shock were supported with centrifugal ventricular assist devices. MEASUREMENTS AND MAIN RESULTS: A total of 15 patients received left ventricular assist devices, five received right ventricular assist devices, and eight received both right and left ventricular assist devices. Mean age of ventricular assistance patients was 50.8 +/- 12.9 yrs (range 22 to 72), and mean duration of ventricular assistance was 2.8 +/- 2.5 days (range 4 hrs to 10 days; median 2 days). Twenty-five complications occurred in 16 patients and included bleeding (13), tamponade (2), systemic embolism (6), seizures (2), and sepsis (2). Nine patients required reexploration for bleeding or tamponade. Nine (32%) of 28 patients were discharged from the hospital. Ventricular assistance for cardiac failure after transplantation was associated with improved survival (p < .10), while age > 50 yrs and postoperative tamponade each showed trends toward association with mortality (p = .10). Survival was not predicted by gender, weight, time on cardiopulmonary bypass, aortic cross-clamp time, urgency of operation, or preoperative congestive heart failure. At 27 +/- 20 months follow-up, all survivors were alive and New York Heart Association functional class I or II. CONCLUSIONS: These results document a low incidence of ventricular assist device use in a surgical practice that employs a relatively simple method of myocardial protection. When postcardiotomy ventricular assistance was necessary, a centrifugal pump was used and successful outcome and satisfactory long-term results were possible in nearly one third of patients. Ventricular assistance for cardiac failure after transplantation was associated with improved survival. Older age is a relative contraindication to mechanical ventricular assistance.

Adult↗