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Biomedical subjects

T J Gardner

Publications and source records attributed to T J Gardner.

At least 73 records · Page 4Linked to original sources
PubMed1993

Reversible postischemic ventricular dysfunction: biochemical insights.

Myocardial stunning, or reversible postischemic ventricular dysfunction, occurs clinically much more frequently than was originally assumed when this phenomenon was first described in experimental studies. Despite the fact that stunned myocardium may appear histologically normal and have a normal metabolic profile, ventricular contractility is severely impaired. In a number of studies using both global and regional stunning models, we have demonstrated impaired oxygen extraction and abnormal patterns of oxygen consumption. In addition, impaired calcium transport or uptake by the sarcoplasmic reticulum occurs and there is sarcolemmal disruption during stunning despite reversibility of the ischemic injury. Although oxygen free radical production is thought to occur only early during postischemic reflow, the use of oxygen radical scavengers in a model of regional stunning was shown to attenuate the ventricular dysfunction.

Animals↗
PubMed1993

Inhibition of neutrophil adherence improves postischemic ventricular performance of the neonatal heart.

BACKGROUND: Reduction of the leukocyte population during postischemic coronary reperfusion results in decreased neutrophil-mediated tissue injury. However, the importance of leukocyte adhesion to coronary endothelium for postischemic ventricular dysfunction after global hypothermic myocardial ischemia is unknown. Neutrophil integrins (CD11b/CD18) upregulate in response to cardiopulmonary bypass and ischemic stress, and their role in generating postoperative ventricular dysfunction was examined in this study. METHODS AND RESULTS: An in vivo, in situ model of neonatal cardiac surgery was established in which neutrophil adherence was manipulated by administering NPC 15669 (an inhibitor of neutrophil CD11b/CD18 surface receptor upregulation). Seventeen 3- to 5-day-old piglets (8 controls and 9 NPC 15669-treated animals) were instrumented with a coronary sinus catheter, sonomicrometry crystals across the short axis of the left ventricle (LV), and a micromanometer positioned in the LV. Hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Myocardial granulocyte accumulation during ischemia and reperfusion was reduced in NPC animals compared with controls (myeloperoxidase activity, 43.4 +/- 2.6 and 75.8 +/- 6.3 mumol/10 mg tissue, respectively; P < or = .005). This was associated with a reduction in coronary vascular resistance in NPC animals compared with controls (P < or = .02) and decreased release of myocardial creatine phosphokinase throughout reperfusion (P < or = .05). NPC animals demonstrated an improved preservation of the end-systolic pressure-volume relation after discontinuation of cardiopulmonary bypass (71 +/- 6% and 96 +/- 6% at 60 minutes, respectively; P < or = .05). There was no difference in ventricular compliance between groups. CONCLUSIONS: These data demonstrate that inhibition of neutrophil CD11b/CD18 surface adherence receptor upregulation reduces granulocyte accumulation in myocardium after hypothermic global ischemia, reduces myocyte damage, and improves ventricular systolic function.

Animals↗
PubMed1993

Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion.

Leukocyte depletion improves early postischemic ventricular performance in neonatal models of global myocardial ischemia. However, the rate of leukocyte reaccumulation after cardiopulmonary bypass and its subsequent impact on myocardial function is not known. This laboratory study examined the effect of leukocyte depletion on myocardial performance during the initial 6-hour period after bypass in an in situ, in vivo porcine model of neonatal cardiac surgery. Fifteen 3- to 5-day-old piglets (eight control and seven leukocyte depleted animals) were instrumented by placement of left ventricular short-axis sonomicrometry crystals and an intraventricular micromanometer catheter. Mechanical leukocyte depletion was achieved with Pall RC100 filters (Pall Biomedical, Inc., Fajardo, Puerto Rico) in the cardiopulmonary bypass circuit. Neonatal hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Two control animals died after the operation and were excluded from data analysis. Leukocyte filtration reduced the granulocyte count during initial myocardial reperfusion to 0.8% of control values. However, circulating granulocyte counts increased in leukocyte depleted animals throughout the postoperative period, reaching 68% of control values by 6 hours. Despite this rapid return of circulating granulocytes, animals subjected to leukocyte depletion had significantly better preservation of left ventricular performance (measured by preload recruitable stroke work, p < or = 0.02), left ventricular systolic function (measured by end-systolic pressure-volume relationship, p < or = 0.05), and ventricular compliance (p < or = 0.04) during the experiment. These changes in ventricular function were associated with a significant increase in left ventricular water content (p < or = 0.02) and tissue myeloperoxidase activity (p < or = 0.005) in control animals compared with leukocyte depleted animals. This study demonstrates that leukocyte depletion during initial reperfusion results in sustained improvement in postischemic left ventricular function despite the rapid return of granulocytes to the circulation.

Animals↗
PubMed1992

Pulmonary embolism in the cardiac surgical patient.

Pulmonary embolism (PE) is thought to occur infrequently after cardiac operations, possibly because systemic heparinization during cardiopulmonary bypass prevents deep vein thrombosis. This retrospective study was undertaken to determine the actual incidence of PE after cardiac operations and to identify risk factors. Between January 1, 1985, and December 31, 1989, 5,694 adult patients (greater than 18 years old) had open heart operations at the Johns Hopkins Hospital. Thirty-two patients (20 men and 12 women) had PE within 60 days of operation, an overall PE incidence of 0.56%. The diagnosis of PE was established by ventilation/perfusion scan, pulmonary angiogram, or autopsy. Mortality among patients with PE was 34%. Using a case-control method, preoperative and postoperative risk factors for PE were identified by multivariate and multiple logistic regression analyses. Preoperative risk factors included bed rest (p less than 0.003), prolonged hospitalization before operation (p less than 0.004), and cardiac catheterization performed through the groin within 15 days before operation (p less than 0.01). Post-operative risk factors were congestive heart failure (p less than 0.008), prolonged bed rest (p less than 0.05), and deep vein thrombosis (p less than 0.03). This study demonstrates that PE is an unusual complication after cardiac operations, has a high mortality rate, and is often related to perioperative immobility and recent groin catheterization. These results also suggest that minimizing preoperative hospital stay may be important in PE prophylaxis.

Bed Rest↗
PubMed1992

Cardiopulmonary bypass and the blood-brain barrier. An experimental study.

The diffuse inflammation produced by cardiopulmonary bypass might disrupt the blood-brain barrier and lead to the transient neurologic dysfunction occasionally seen after cardiac operations. To evaluate this possibility, blood-brain barrier integrity was measured by carbon 14-aminoisobutyric acid tracer technique after 2 hours of cardiopulmonary bypass in piglets. Six animals were cooled to 28 degrees C on cardiopulmonary bypass and then rewarmed to 38 degrees C before carbon 14-aminosisobutyric acid was injected intraarterially. A control group of six animals underwent median sternotomy and heparinization but were not placed on cardiopulmonary bypass. Blood-to-brain transfer coefficients for carbon 14-aminosisobutyric acid were calculated for multiple brain regions; higher coefficients reflect greater flux of carbon 14-aminosisobutyric acid and suggest loss of blood-brain barrier integrity. The brain regions examined and their transfer coefficients (cardiopulmonary bypass versus control mean +/- standard error of the mean ml/gm/min) were middle cerebral artery territory cortex (0.0032 +/- 0.0002 versus 0.0030 +/- 0.0002; p = 0.42), diencephalon (0.0031 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.50), midbrain (0.0028 +/- 0.0002 versus 0.0027 +/- 0.0002; p = 0.86), cerebellum (0.0036 +/- 0.0003 versus 0.0029 +/- 0.0002; p = 0.22), and spinal cord (0.0035 +/- 0.0003 versus 0.0041 +/- 0.0008; p = 0.48). There were no significant differences in transfer coefficients between animals placed on cardiopulmonary bypass and control animals in any brain region examined. The pituitary gland lacks a blood-brain barrier and had a correspondingly high coefficient in control animals and those undergoing cardiopulmonary bypass (0.077 +/- 0.012 versus 0.048 +/- 0.008; p = 0.07). Two hours of moderately hypothermic cardiopulmonary bypass does not disrupt the blood-brain barrier.

Aminoisobutyric Acids↗
PubMed1991

Current indications, risks, and outcome after pericardiectomy.

A retrospective analysis of the records of 60 patients who underwent pericardiectomy over a 10-year period (1980 to 1990) at The Johns Hopkins Hospital was performed. Indications for operation were effusive disease in 24 patients and constriction in 36 patients. Six patients (10%) with pericardial effusion had pain as the primary symptom necessitating intervention. The operative approach for pericardiectomy was median sternotomy in 52 patients (4 patients required cardiopulmonary bypass) and left anterior thoracotomy in 8 patients. Nine patients (5 with constriction and 4 with effusion) with a prior limited pericardial procedure required formal pericardiectomy. The operative mortality rate for pericardial effusion and constriction was 4.2% and 5.6%, respectively. Follow-up (median follow-up, 56.9 +/- 38.2 months) was obtained on 56 patients (93.3%). Actuarial survival at 1 year, 5 years, and 10 years for all patients was 82.1% +/- 5.1%, 71.7% +/- 6.7%, and 59.8% +/- 12.2%, respectively. A Cox proportional hazards regression analysis was performed using 20 clinical variables. A history of malignancy, previous pericardial procedure, and preoperative New York Heart Association class IV were found to be predictors of poor survival. All patients who underwent operation primarily for effusion with associated pain are alive and have improved functional capacity without steroid use. We conclude that pericardiectomy can be performed with low mortality and can result in good long-term survival and improved functional capacity. Patients who are seen primarily with pain refractory to steroid therapy can be relieved of symptoms with operation.

Actuarial Analysis↗
PubMed1990

Surgical standby for percutaneous transluminal coronary angioplasty: a survey of patterns of practice.

To determine patterns of surgical standby for percutaneous transluminal coronary angioplasty (PTCA), a questionnaire was mailed to 196 US institutions in which PTCA and coronary artery bypass grafting (CABG) are performed regularly. Eighty-nine responses (46%) were received and comprise this report. Of responding institutions, the mean number of hospital beds was 615. In 1987, these institutions performed a mean of 337 PTCAs and 558 open-heart surgical procedures. The rate of emergency CABG for PTCA complications (occlusion, dissection, or coronary perforation) was 4.4% +/- 0.3%, whereas the rate of urgent CABG (within 24 hours) for PTCA failure was 3.7 +/- 0.6%. The incidence of emergency CABG for PTCA complications was higher (5.1% +/- 0.6%) among low-volume PTCA centers (less than 250 cases per year) than at high-volume centers (more than 250 cases per year) (3.7% +/- 0.3%; p less than 0.05). The most common pattern of surgical backup was to maintain an open operating room on standby (57/89, 64%), and the second most common pattern was to make the next open operating room available, allowing operating room access within 1 to 3 hours (21/89, 24%). Nearly a third of institutions (26/89, 29%) maintained a flexible backup arrangement according to PTCA risk. Routine pre-PTCA patient evaluation by surgeon and/or anesthesiologist occurred in 38% (34/89). Fees for standby services were charged by 51% of surgical teams (45/89), 39% of anesthesia teams (35/89), and 38% of operating room facilities (34/89).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1990

Routine use of the left internal mammary artery graft in the elderly.

Left internal mammary artery (LIMA) grafts have better long-term patency rates than do saphenous vein grafts and result in improved late survival. The present study was undertaken to assess the results of LIMA grafting in the elderly. From 1980 through 1988, 723 patients 70 years of age or older had isolated coronary artery bypass grafting performed. During the first 5 years, only 11% of the elderly patients received LIMA grafts, whereas 86% having coronary artery bypass grafting since 1985 had LIMA grafts. Since 1986, LIMA use in the elderly has become routine, with 92% of patients receiving internal mammary artery grafts. During the first 5 years, elderly patients had a hospital mortality rate of 9.3%. Since 1985, the hospital mortality rate fell to 5.5%. In addition, the occurrence of major surgical complications was either unchanged or reduced in patients receiving LIMA grafts. Furthermore, late follow-up indicates a significantly improved 4-year survival rate in patients with internal mammary artery grafts compared with those without: 86 +/- 0.02% versus 77 +/- 0.03% (p less than 0.01). Analysis of multiple potential risk factors for early mortality was performed using multiple logistic regression and late survival using the Cox proportional hazards model. Although unmeasured predictor variables may confound retrospective analyses, LIMA grafting appears to be an independent predictor both of improved early and late survival.

Aged↗
PubMed1990

Long-term results of total repair of tetralogy of Fallot in childhood.

Between 1958 and 1977, 170 children aged 10 years or less underwent total repair of tetralogy of Fallot at The Johns Hopkins Hospital. Follow-up data were obtained on 128 (90%) of the 143 who survived the operation at 10 to 28 years postoperatively (mean follow-up, 18 years). All patients completed an extensive questionnaire, and 59 returned for a thorough evaluation consisting of a history and physical examination, electrocardiogram, 24-hour Holter monitoring, exercise stress testing, pulmonary function testing, and two-dimensional and Doppler echocardiography. Late survival was excellent with only two of four known late deaths due to cardiac-related causes and with all 59 patients in New York Heart Association class I or II. None had cyanosis or clubbing. Normal sinus rhythm was present in 90%. One patient had complete heart block, and 75% had right bundle-branch block on the electrocardiogram. Right ventricular function was normal by echocardiography in 78%. Residual mild to moderate pulmonary stenosis was noted by Doppler study in 8 patients. Pulmonary regurgitation was present in 78%, but in only 11 patients was it graded as moderate and in none was it severe. Stress testing documented the excellent functional status of most patients, with 92% of predicted exercise time and 94% of maximum heart rate being attained. In the few who had impaired cardiac performance, this correlated best with moderate pulmonary regurgitation. Although the overall late functional status of patients undergoing repair in the first decade of life was very good, these patients need continued follow-up to assess the severity of pulmonary regurgitation and the need of possible intervention.

Adult↗
PubMed1990

The effective treatment of postpericardiotomy syndrome after cardiac operations. A randomized placebo-controlled trial.

Although the postpericardiotomy syndrome is a common complication of cardiac operations, the most effective drug regimen for the treatment of this condition has not been established. The present study was designed to evaluate the effectiveness of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of postpericardiotomy syndrome, in a double-blind, placebo-controlled randomized trial with a 10-day course of ibuprofen or indomethacin. Of 1019 adult patients undergoing cardiac operations during a 14-month period, a diagnosis of postpericardiotomy syndrome was made in 187, and 149 were enrolled in the study. Diagnosis was based on the presence of at least two of the following: fever, anterior chest pain, and friction rub. Drug efficacy was defined as the resolution of at least two of these criteria within 48 hours of drug initiation. Ibuprofen and indomethacin were 90.2% and 88.7% effective, respectively, and both were significantly more effective than placebo (62.5%, p = 0.003). The occurrence of side effects, including nausea, vomiting, renal failure, and fluid retention, was low in all groups (13.1% for ibuprofen, 16.1% for indomethacin, and 16.7% for placebo [p = not significant). Length of hospital stay, incidence of ischemic events, and accumulation of significant pericardial effusions were similar in all groups. The results of this study demonstrate that both ibuprofen and indomethacin provide safe and effective symptomatic treatment for postpericardiotomy syndrome.

Cardiac Surgical Procedures↗
PubMed1989

Exploratory analysis of time-dependent risk for infection, rejection, and death after cardiac transplantation.

Data from 95 heart transplantations performed at The Johns Hopkins Hospital from July 1983 to October 1988 were analyzed to detect patterns of morbidity and mortality. Using nonparametric techniques, hazard functions were determined for all deaths and for deaths due to infection or rejection. The rates of rejection and infection (episodes per patient-month) were determined within each of ten intervals following transplantation. A total of 19 deaths, 281 rejection episodes, and 180 distinct infections were available for analysis during a follow-up of 1 to 62 months. The hazard function for rejection appeared biphasic, with a rapidly decelerating early phase during the first year followed by a constant late phase. The hazard function for infection was triphasic, with a delayed, decelerating early phase, a period of increased risk approximately 2 years after operation, and finally a late constant phase. Both infection and rejection rates (episodes per patient-month) were biphasic, with rapidly decelerating early phases and constant late phases. Multiple regression analysis demonstrated that eventually nonsurviving patients had significantly higher rates of rejection and infection during both the early and late phases compared with survivors. The increased rate of rejection among nonsurvivors was evident throughout follow-up, although no deaths were attributable directly to rejection after the first 8 months. These data suggest that a complex interrelationship between infection and rejection determines late survival after cardiac transplantation and that aggressive treatment of late rejection predisposes toward death from infection.

Actuarial Analysis↗
PubMed1989

Does hypothermic fibrillatory arrest improve myocardial protection during emergency revascularization?

Hypothermic fibrillatory arrest (HFA) was compared with conventional hypothermic cardioplegic arrest (HCA) in a model of acute regional ischemia. In 20 pigs, the left anterior descending coronary artery was occluded for 30 minutes before cardiopulmonary bypass. In the HCA group (n = 10), the heart was arrested with a hyperkalemic cold crystalloid solution, whereas in HFA animals (n = 10), the heart was vented and allowed to fibrillate spontaneously without cross-clamping. Miniature pH probes monitored intramyocardial pH during 45 minutes of arrest (HCA or HFA, both with systemic and topical myocardial cooling) and during two hours of coronary reperfusion. Hypothermic fibrillatory arrest did not ameliorate the acidosis in the ischemic (left anterior descending) region; indeed, after two hours of coronary reperfusion, there was a trend toward more acidosis in the postischemic left anterior descending territory in the HFA group. However, HFA did prevent acidosis in the nonischemic (left circumflex) territory. Infarct size expressed as percent of region at risk was 18.1% +/- 3.2% (mean +/- standard error of the mean) in the HCA animals and 18.8% +/- 4.4% in the HFA animals. These results demonstrate that HFA offers no advantage over HCA in protection of regionally ischemic myocardium in a model with minimal collateral circulation.

Animals↗
PubMed1989

Cardiopulmonary bypass with profound hypothermia. An optimal preservation method for multiorgan procurement.

Numerous techniques have been devised for the harvesting of individual organs during a multiorgan procurement operation. Cardiopulmonary bypass with profound hypothermia (PH) has been employed in successful harvesting of heart-lung, kidney, pancreas, and liver grafts. This report summarizes our experience using CPB-PH for the harvesting of multiple organs from 10 brain-dead donors during the period from July 1983 to January 1988. Organs harvested included 10 heart-lungs, 17 kidneys (3 kidneys were not harvested due to anatomy and elevated creatinine), 1 liver, and 1 pancreas. Mean ischemic time for the distantly procured heart-lung grafts was 281 +/- 10 min. Adequate pulmonary function, as assessed by arterial blood gases, was observed in each heart-lung recipient (mean PO2 was 119 +/- 46 mmHg, 164 +/- 47 mmHg, 130 +/- 30 mmHg, 114 +/- 26 mmHg at immediate post-CPB, 6 hr postop, 24 hr postop, and postextubation, respectively). Mean length of intubation was 34 +/- 8 hr. Mean creatinines of kidney recipients at days 2, 7, and current creatinine were 7.4 +/- 3.6 mg%, 3.6 +/- 2.4 mg%, and 1.6 +/- 0.66 mg%, respectively. Eight kidney recipients (47%) required dialysis, (2 patients required only a single dialysis). Ninety-four percent of the kidney transplant patients are alive, and 88% (15/17) have functioning kidneys. One liver and 1 pancreas were harvested during this time period. Preservation was satisfactory in both the pancreas (Johns Hopkins Hospital) and liver (Dr. Thomas Starzl, personal communication). The technique of CPB-PH has resulted in excellent function of heart-lung grafts. Follow-up of the transplanted kidneys, liver, and pancreas utilizing this technique shows equal or better function compared with standard techniques. This technique offers other advantages in addition to satisfactory multiorgan preservation. Placement of an unstable patient on CPB ensures adequate organ perfusion and allows for a gradual yet uniform cooling of all organ systems. Cooling to a core temperature of 10-15 degrees C requires 30 min, during which time preliminary intraabdominal and mediastinal dissection can be carried out. Following cessation of CPB and subsequent exsanguination, organs can be more easily dissected in a near-bloodless field. This technique does not preclude additional crystalloid organ flushing. Since multiorgan procurement occurs with virtually every donor, this technique may be the optimal method providing excellent preservation, ease of dissection, and better control of hemodynamics during the operation.

Cardiopulmonary Bypass↗
PubMed1989

The risk of coronary bypass surgery for patients with postinfarction angina.

Three hundred consecutive patients who developed unstable postinfarction angina requiring isolated coronary artery bypass from 1982 through 1987 were analyzed. Hospital mortality was 5%; 15 (5.5%) additional late deaths occurred during the 69-month follow-up period (mean follow-up, 23.3 months). Significant independent predictors of perioperative mortality by univariate analysis were ejection fraction (p = 0.004); existence of an anterior, transmural infarction (p = 0.0001); and the requirement for preoperative intra-aortic balloon counterpulsation (p = 0.001). By multivariate analysis, only the occurrence of an anterior, transmural infarction (p = 0.001) and the preoperative use of an intra-aortic balloon pump (p = 0.004) were significant independent predictors of mortality. Actuarial survival in this group ranged from 96 +/- 1% at 1 year to 88 +/- 4% at 5 years.

Actuarial Analysis↗
PubMed1989

Systolic and diastolic left ventricular dysfunction due to mild hypothermia.

Postoperative cardiac patients frequently are mildly hypothermic, yet the influence of hypothermia on left ventricular (LV) contractility has received little attention. To study the possible effects of mild hypothermia on LV function, six pigs were placed on partial right ventricular bypass, the hearts were electrically paced to control heart rate, and myocardial temperature was varied between 34 degrees and 38 degrees C. Using two pairs of orthogonally oriented sonomicrometer crystals in the left anterior descending (LAD) and left circumflex (LCX) distributions, we estimated regional work (the area within LV pressure-area loops) over a range of LV preloads. Diastolic function was assessed by measurement of the time constant of LV pressure decay during isovolumic relaxation. Regional work data were expressed as percentages of baseline (38 degrees C and end-diastolic pressure of 10 mm Hg). To control for preload variations, regional work and time constants were calculated from beats with end-diastolic areas within 0.1% of baseline. Regional work (mean +/- SEM) declined from 85.1 +/- 6.7% at 38 degrees C to 31.9 +/- 4.4% at 34 degrees C. Time constants were prolonged from 44.8 +/- 2.5 msec at 38 degrees C to 61.6 +/- 2.7 msec at 34 degrees C. These data demonstrate a marked depression of LV contractility, even at mild levels of hypothermia that may be encountered clinically after cardiac operations.

Animals↗