Biomedical subjects
L A Golding
Publications and source records attributed to L A Golding.
In vivo hemodynamic performance of the Cleveland Clinic CorAide blood pump in calves.
BACKGROUND: The Cleveland Clinic CorAide left ventricular assist system is based on a small implantable continuous-flow centrifugal blood pump with a completely suspended rotating assembly designed for long-term circulatory support (5 to 10 years). METHODS: Between June 1999 and August 2000, the CorAide blood pump was implanted in 10 calves for 1 month and in 3 calves for 3 months. RESULTS: The mean pump flow and arterial pressure were 6.1 +/- 1.1 L/min and 97 +/- 5 mm Hg, respectively. The mean plasma free-hemoglobin level after postoperative day 3 was 2.0 +/- 1.8 mg/dL. Renal and hepatic function remained normal in all cases. There was no incidence of mechanical failure, hemolysis, bleeding, or systemic organ dysfunction in any of the cases. Significant findings at autopsy were limited to two cases of renal infarction, one of which was associated with an outflow graft infection. CONCLUSIONS: The CorAide blood pump is easily implanted, reliable, nonhemolytic, and nonthrombogenic, positioning it as a leading third-generation, continuous-flow left ventricular assist system with a completely suspended rotor.
Cleveland clinic rotodynamic pump.
BACKGROUND: It is now accepted that 70% to 80% of patients with end-stage heart failure would benefit from a permanent implanted left ventricular assist device. Previously there was little consideration of the use of nonpulsatile pumps for this function. METHODS: An extensive 5-year engineering research and development program to develop a permanent implanted nonpulsatile blood pump has been undertaken. RESULTS: We have developed a continuous-flow blood pump of small size (207 g) and low power requirement (6.5 watts) producing 5 L/min flow with low hemolysis. CONCLUSIONS: This pump has the potential to be the basis of an innovative ventricular assist system.
Chronic nonpulsatile blood flow. II. Hemodynamic responses to progressive exercise in calves with chronic nonpulsatile biventricular bypass.
We investigated the effects of stepwise treadmill exercise on animal (calf) hemodynamic variables during chronic nonpulsatile biventricular bypass with ventricular fibrillation. Seven days was allowed for recovery from the effects of anesthesia and surgery; each animal's natural heart was then fibrillated. The pump flows were maintained at nominal rates of 90, 100, and 120 ml.kg-1.min-1 for 1 week each, with the order varying from experiment to experiment. A total of 30 incremental exercise tests were performed on five animals. No significant changes in mean aortic pressure were observed during nonpulsatile perfusion at the three nominal flow rates of nonpulsatile flow either before or during exercise. The systemic vascular resistance decreased significantly during exercise (from 705 +/- 22 to 547 +/- 81 dyne.sec.cm-5, p < 0.01, and from 604 +/- 25 to 510 +/- 15 dyne.sec.cm-5, p < 0.05, at nominal flow rates of 100 and 120 ml.kg-1.min-1, respectively). There were also significant (analysis of variance, Scheffe test, p < 0.05) differences in systemic vascular resistance among three nominal flow rates both before and during exercise. These results suggest that the autonomic nerve reflex control of the cardiovascular system in physical exercise was functioning normally in animals with chronic nonpulsatile blood flow.
Chronic nonpulsatile blood flow. III. Effects of pump flow rate on oxygen transport and utilization in chronic nonpulsatile biventricular bypass.
The relationship between blood flow and oxygen transport was studied in five calves with chronic nonpulsatile biventricular bypass. Seven days was allowed for recovery from the effects of anesthesia and operation; the natural heart was then fibrillated. Pump flows were maintained at nominal rates of 90, 100, or 120 ml.kg-1.min for 1 week each, with the sequence varied from experiment to experiment. Venous and arterial blood samples were taken at rest for blood gas analysis. Serum lactate analysis was done twice a week, on the third and seventh days after each pump flow change. Serum catecholamine levels were assayed on the seventh day of each flow rate. Progressive exercise tests were also conducted during each test segment. Basal oxygen consumption of a 4-month-old calf was 6.3 +/- 0.3 ml.kg-1.min-1. The mixed venous oxygen tension decreased when pump flow rate was reduced (29.6 +/- 1.0, 28.3 +/- 1.2, and 23.8 +/- 0.9 mm Hg at 120, 100, and 90 ml.kg-1.min-1 of pump flow, respectively), and oxygen extraction increased linearly when pump flow rate was reduced. Hemoglobin concentration significantly affected oxygen extraction rate. Serum lactate concentration increased significantly at a 90 ml.kg-1.min-1 perfusion compared with concentrations at other pump flow rates (7.81 +/- 2.42 mEq/L at 90 ml.kg-1.min-1 vs 0.71 +/- 0.19 and 0.73 +/- 0.81 mEq/L at 100 and 120 ml.kg-1.min-1, respectively; p < 0.01, analysis of variance, Scheffe F test). Maximum oxygen extraction during exercise was 78%. These results suggest that a critical flow level between 90 and 100 ml.kg-1.min-1 maintains oxidative metabolism in the calf with chronic nonpulsatile flow. The resulting oxygen delivery was slightly higher than that indicated in the literature. Maximal oxygen extraction was normal.
The Cleveland Clinic rotodynamic pump program.
The Cleveland Clinic Foundation has developed a unique rotodynamic blood pump for future use as a permanent implant. This pump is small (2.5 x 2.5 inches) and requires an electric input power of 7 watts to produce 5 L/min of blood flow against 100 mm Hg at 3,000 rpm. Initial in vivo testing has confirmed in vitro function and shown low hemolysis. Endurance bench testing has exceeded 12 months of continuous function. This pump is the basis of an innovative ventricular assist system in which power is supplied by a tranocutaneous electrical transmission system, and pacer technology is used for both control logic and telemetry functions. The resulting system will be completed and tested under an NHLBI contract during the next 5 years.
Blood coagulability and hematological changes in calves with chronic centrifugal biventricular bypass pumps.
A Hemadyne centrifugal pump was used to determine the effects of long-term circulatory assist on platelet number and aggregability. Five calves were supported on biventricular bypass with a pair of Hemadyne centrifugal pumps. On the 7th postoperative day (POD), the heart was fibrillated after pump flow rates were increased to compensate for the total cardiac output. The animals were anticoagulated with heparin throughout the study and adjustments were made to maintain the activated clotting time at between 180 and 220 sec. To maintain the activated clotting time level in the therapeutic range, it was necessary to gradually increase the heparin dose with time due to the developing heparin tolerance. Fibrinogen levels increased significantly on the 3rd postoperative day when compared to the preoperative control value. Platelet aggregation was measured using a whole blood impedance method with adenosine diphosphate and collagen as agonists. Platelet function was found to be significantly depressed following the biventricular bypass procedure (P < 0.05 on the 7th, 14th, and 21st POD). Platelet numbers were significantly decreased compared to the preoperative control values, being the lowest on the 1st and 3rd POD, recovering to 76% of the control values by the 7th POD, and then gradually decreasing to the 55% level by the 28th POD. These results show that, when tested for up to 4 weeks following surgery, both platelet number and function in calves supported with centrifugal pumps remain depressed. Despite the progressive heparin tolerance and suppressed platelet number and function, none of the animals showed abnormal bleeding tendencies on biventricular bypass.
Chronic nonpulsatile blood flow. I. Cerebral autoregulation in chronic nonpulsatile biventricular bypass: carotid blood flow response to hypercapnia.
To investigate the response of the carotid blood flow and general circulation to hypercapnia in chronic nonpulsatile blood flow, we performed 18 carbon dioxide gas inhalation studies on three calves undergoing a centrifugal biventricular bypass with ventricular fibrillation. An ultrasonic flow probe was put on the carotid artery during biventricular bypass pump implantation, and pump flows were maintained at 90, 100, and 120 ml/kg per minute for 1 week each. The carbon dioxide inhalation studies were performed twice a week. Hypercapnia was induced by administering pure carbon dioxide gas through a nasal tube at flow rates of 0, 5, 7.5, 10, 12.5, and 15 L/min for 5 minutes each at three different nominal pump flow rates, and the resultant arterial blood gas and hemodynamic changes were recorded. No significant correlation existed between the carotid blood flow and mean aortic pressure, which varied from 70 to 140 mm Hg, but the carotid blood flow correlated significantly (p < 0.01) with the systemic pump flow rate. A significant (p < 0.01) linear relationship was found between the carotid blood flow and arterial carbon dioxide tension. For each 1 mm Hg change in arterial carbon dioxide tension, there was a 2.8 % change in the carotid blood flow. The percent changes in the carotid blood flow in response to arterial carbon dioxide tension were calculated as 2.9%, 3.7%, and 2.5% for each 1 mm Hg change in arterial carbon dioxide tension at pump flows of 90, 100 and 120 ml/kg per minute. No significant differences in the carotid blood flow response to hypercapnia were detected among the three systemic pump flow rates. These results thus suggested that chronic nonpulsatile blood flow had no detrimental effects on cerebral autoregulation.
The Cleveland Clinic-Nimbus total artificial heart. In vivo hemodynamic performance in calves and preclinical studies.
In vitro function of the Cleveland Clinic-Nimbus electrohydraulic total artificial heart met National Heart, Lung, and Blood Institute hemodynamic guidelines for such devices. In a series of in vivo experiments, we implanted the total artificial heart in eight calves (mean weight 87 kg), one for a short-term experiment and seven for long-term experiments. The mean blood flow during support was 7.7 +/- 1.6 L/min with left atrial pressure 13 +/- 6 mm Hg, right atrial pressure 13 +/- 4 mm Hg, and aortic pressure 97 +/- 9 mm hg. Maximum pump flow (9.6 L/min) occurred after 4 days of support as a result of the high resting cardiac output of the animals. A 10% to 15% right pump stroke-volume limit effectively balanced atrial pressures, and afterload insensitivity was confirmed by the in vivo studies. Calves tolerated treadmill exercise studies well, with an average duration of 22 minutes and an average top speed of 2.1 mph. The experiments were terminated after 1 day to 120 days of support (mean 32 days). Most experiments were terminated as a result of correctable mechanical problems. In a separate study of six adult human patients undergoing orthotopic cardiac transplantation, five showed an excellent fit for the Cleveland Clinic-Nimbus total artificial heart. Further studies using chest roentgenograms, chest measurements, and transesophageal echocardiography should help predict fit of the total artificial heart in potential candidates. Initial candidates for a "vented-electric" version of the Cleveland Clinic-Nimbus total artificial heart are patients for whom univentricular (left ventricular assist device) support is not appropriate, but who require mechanical support as a bridge to cardiac transplantation.
Catastrophic vasoconstriction after protamine reversal of heparin anticoagulation in the goat.
Catastrophic pulmonary vasoconstriction after protamine reversal of heparin anticoagulation was observed frequently in goats that underwent centrifugal biventricular bypass pump implant. Care should be taken when protamine is used to reverse heparin anticoagulation in goats.
Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study.
We tested the efficacy and safety of aprotinin in 169 patients undergoing isolated reoperative myocardial revascularization. Patients were randomly assigned to high-dose aprotinin, low-dose aprotinin, or placebo treatment groups in a double-blind, placebo-controlled study. Treatment groups did not differ significantly with respect to age, sex, red cell mass, number of grafts, use of internal thoracic artery, or incidence of preoperative aspirin therapy. Patients treated with aprotinin had a significant reduction in postoperative chest tube drainage (720 +/- 753, 866 +/- 1,636, and 1,121 +/- 683 mL, respectively, for high-dose aprotinin, low-dose aprotinin, and placebo; p < 0.001). Transfusion requirements were reduced in aprotinin-treated patients (2.1 +/- 4.2, 4.8 +/- 11.8, and 4.1 +/- 6.2 units for high-dose, low-dose, and placebo, respectively; p < 0.001). A similar reduction in chest tube drainage and transfusion requirements was seen in patients using aspirin preoperatively. Q-wave myocardial infarctions were increased in the aprotinin subgroups (17.5%, 14.3%, and 8.9% for high-dose, low-dose, and placebo groups; not significant). Acute vein graft thrombosis was found in six of 12 vein grafts studied at postmortem examination in patients receiving aprotinin but not in any of five grafts in patients receiving placebo. We conclude that aprotinin is extremely effective in reducing bleeding and transfusion requirements and may increase the risk of graft thrombosis.
Postcardiotomy centrifugal mechanical ventricular support.
From August 1979 through August 1991, 91 patients were supported with centrifugal mechanical ventricular assist. Major indications for its use were postcardiotomy ventricular failure (79) or as a bridge to cardiac transplantation (12). In postcardiotomy use (0.2% of all cardiac procedures), there were 54 male (68.4%) and 25 female patients (31.6%) with a mean age of 54.8 years and a mean duration of use of 3.56 days (range, 1 hour to 19 days). Forty-nine patients (62%) were successfully weaned, and 20 (25.3%) were hospital survivors. In 57 patients the device was inserted to wean from cardiopulmonary bypass, whereas in 22 it was employed later in the postoperative period because of low cardiac output or sudden arrest. Thirty-four (59.6%) of the 57 patients in the former group were weaned, and 15 (26.3%) were discharged, results similar to those in the latter group with 15 (68.2%) weaned and 5 (22.7%) discharged. Morbidity associated with use of centrifugal blood pumps included bleeding (87.3%; mean transfusion requirement, 53.2 units), renal failure (46.8%), cerebrovascular accident (12.7%), thromboembolism (12.7%), and hepatic insufficiency (12.7%). After a mean follow-up of 45.4 months (range, 2 to 142 months), 7 patients had died (35% late mortality), 1 patient is in functional class IV, and all others are in functional class I or II. Lower survival was associated with biventricular failure and renal failure but not with age or sex of the patient.
Treatment of cardiogenic shock with the Hemopump left ventricular assist device.
A multiinstitutional study is in progress to evaluate the Hemopump in the treatment of cardiogenic shock. Fifty-three patients with refractory cardiogenic shock were selected for Hemopump assistance. The hemodynamic definition of cardiogenic shock included (1) a cardiac index of less than 2.0 L.min-1.m-2, (2) pulmonary capillary wedge pressure of greater than 18 mm Hg, and (3) a systolic blood pressure of less than 90 mm Hg or a left ventricular work index of less than 1,500 g-m.m-2.min-1. The Hemopump was successfully inserted in 41 of 53 patients (77.3%). A significant improvement in the hemodynamic status was seen during Hemopump assistance. A minimal level of hemolysis was observed. No leg ischemia was observed. The 30-day overall survival of the Hemopump group was 31.7%. Criteria establishing indications for use and clinical utility are proposed. We conclude that the Hemopump provides significant hemodynamic support of the patient in cardiogenic shock allowing for recovery from ventricular stunning in marginal ventricles, and that in select patients the Hemopump may offer a major improvement in survival over conventional therapy.
CNS effects on cardiomyoplasty in goats: preliminary study.
Following cardiomyoplasty, the latissimus dorsi (LD) muscle contracts in response to both pacemaker and central nervous system (CNS) derived action potentials. To evaluate the effect of this dual stimulation on cardiac function, six goats (56 kg to 80 kg) underwent treadmill tests 4 to 5 months after surgery. Sonomicrometer crystals were used to measure changes in the left ventricular short-axis dimension (LVSAD) and regional length changes in the LD muscle. Pacing mediated stimulation resulted in 17 +/- 4% fractional shortening of the muscle pedicle lasting 400 +/- 17 msec. Walking at speeds of 0.8 and 2.4 km/hr produced muscle contractions of variable duration and intensity. LVSAD was decreased by both pacing (14%) and walking (up to 10%). Pacing in combination with walking caused erratic muscle contractions with concomitant changes in LVSAD suggestive of impaired ventricular filling. No arrhythmias were noted during exercise.
Postcardiotomy mechanical support.
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J. Maxwell Chamberlain memorial paper. Sternal wound complications after isolated coronary artery bypass grafting: early and late mortality, morbidity, and cost of care.
Of 6,504 consecutive patients who underwent isolated coronary bypass grafting in 1985 to 1987, 72 (1.1%) patients experienced sternal wound complications. Ten patients (14%) with wound complications died of multi-system failure. Only the patients with negative cultures fared well; of the bacterial culture categories, polymicrobial infection carried the worst prognosis. Effects of recurring infection were seen throughout the first year. Patients, grouped according to conduits received, experienced these wound complication rates: vein grafts only, 11/1,085 (1.0%); one internal thoracic artery, 38/4,073 (0.9%); and bilateral internal thoracic artery grafts, 23/1,346 (1.7%). There were no significant differences in wound complication rates between primary and reoperation patients or among conduit groups. By logistic regression analysis, the relative risk for patients with diabetes and bilateral internal thoracic artery grafting was 5.00 (95% confidence interval, 2.4 to 10.5). Operation time as a continuous variable increased the relative risk of wound complication 1.47 times per hour (1.3 to 1.7); obesity, 2.90 times (1.8 to 4.8); and blood units as continuous variable, 1.05 times per unit (1.01 to 1.10). Bilateral internal thoracic artery grafting in nondiabetic patients carried no greater risk of wound complication than that in patients with vein grafts only or with one internal thoracic artery graft.
Comparison of brachial and radial arterial pressure monitoring in patients undergoing coronary artery bypass surgery.
The pressure in either the radial (n = 88) or proximal brachial artery (n = 82) was compared with aortic pressure before and after cardiopulmonary bypass (CPB) in patients receiving coronary artery bypass grafts. Radial artery pressures were measured via 20-G 5-cm long catheters, brachial artery pressures via 20-G 12.7-cm catheters, and aortic pressures were measured via a luer port in the aortic perfusion cannula. Transducers were connected via 122-cm long tubing. For the various systems, mean natural frequencies were 16.1 to 17.7 Hz and damping coefficients were 0.16 to 0.27. Before CPB the brachial systolic, diastolic, and mean pressures were 108.2 +/- 5.2%, 100.9 +/- 2.8%, and 99.6 +/- 2.3% of aortic; respective radial pressures were 113.9 +/- 9.6%, 99.5 +/- 2.8%, and 98.4 +/- 2.8% of aortic. Immediately after CPB the brachial pressures were 99.5 +/- 7.5%, 98.9 +/- 3.5%, and 97.4 +/- 2.9% of aortic, whereas respective radial pressures were 92.1 +/- 14.6%, 94.7 +/- 5.6%, and 90.8 +/- 7.4%. All brachial and radial as a per cent of aortic pressure medians were significantly different, and except for prebypass diastolic and mean, the variance for brachial pressures was significantly less than that for pressures in the radial artery. The prebypass brachial correlation (r) with aortic for systolic, diastolic, and mean were 0.90, 0.98, and 0.98; respective radial correlations with aortic were 0.78, 0.97, and 0.95. Postbypass brachial systolic, diastolic, and mean correlations were 0.91, 0.97, and 0.98; radial were 0.50, 0.93, and 0.83. Brachial artery pressures were more accurate and reliable than radial artery pressures.
Reoperation for coronary atherosclerosis. Changing practice in 2509 consecutive patients.
We analyzed trends in clinical, angiographic, and operative variables and documented long-term survival in 2509 consecutive patients who underwent reoperation for myocardial revascularization at The Cleveland Clinic during a 20-year period (1967 to 1987). The patients were grouped into four cohorts by year of surgery. This analysis showed that vein graft atherosclerosis has become the leading indication for reoperation, and patient age and interval between operations continue to increase. Mortality rates ranged from 2% to 5% and, despite increasing comorbidity, more extensive coronary atherosclerosis, and worse left ventricular function, the hospital mortality rate was 2.9% from 1985 to 1987. Perioperative new Q-wave myocardial infarction occurred in 7% to 8% of patients from 1967 to 1984 but decreased to 4% in the 1985 to 1987 period (p = 0.04). Internal thoracic artery graft usage in reoperations increased from 27% in the 1967 to 1978 period to 67% in the 1985 to 1987 period. Advanced age and presence of left main coronary artery disease adversely influenced late survival more consistently than other factors. Patients operated on in 1967 to 1978 had fewer risk factors, which explains their higher survival rate compared with more recent cohorts. Factors associated with improved 10-year actuarial survival included age younger than 65 years, mild angina, no major comorbidity, no left main coronary artery disease, good left ventricular performance, and an internal thoracic artery graft.