Combined Registry for the Clinical Use of Mechanical Ventricular Assist Pumps and the Total Artificial Heart in conjunction with heart transplantation: sixth official report--1994.

BACKGROUND: The Combined Registry has existed since 1985 with a design toward the voluntary submission of data from centers undertaking mechanical circulatory assistance. METHODS: The compiled results of the Combined Registry for the Clinical Use of Mechanical Ventricular Assist Pumps and the Total Artificial Heart was reviewed and subjected to strict statistical evaluation. RESULTS: More than 2000 implanted devices have been reported through January 1994, and 584 of these have been placed with the intention of bridge to heart transplantation. Nearly 70% of these patients have subsequently undergone heart transplantation, and 69% of those patients have survived to discharge from the hospital. Outcome statistics continue to favor isolated left ventricular support, although only discharge rates are significantly improved over right (p = 0.01) or biventricular assistance (p < 0.001) and the total artificial heart (p < 0.001). Within the group of left ventricular devices no individual mode of support proved advantageous over the others for transplantation or discharge rates. The 30-day mortality for all devices is approximately 36%, which remains much higher than that for orthotopic heart transplants. Isolated left ventricular support, however, had a 30-day mortality of only 9% with similar improvement in 12- and 24-month survival. CONCLUSIONS: These data show the continued success with these devices for bridging critically ill patients to transplantation. Additionally, it supports the ongoing development of devices implanted for long-term use, which might replace orthotopic transplantation for those patients currently deemed marginal candidates.

Acute, subacute, and subchronic oral toxicity studies of 1,1-dichloroethane in rats: application to risk evaluation.

1,1-Dichloroethane (DCE) is a solvent that is often found as a contaminant of drinking water and a pollutant at hazardous waste sites. Information on its short- and long-term toxicity is so limited that the U.S. EPA and ATSDR have not established oral reference doses or minimal risk levels for the volatile organic chemical (VOC). The acute oral LD(50) in male Sprague-Dawley (S-D) rats was estimated in the present study to be 8.2 g/kg of body weight (bw). Deaths appeared to be due to CNS depression and respiratory failure. In an acute/subacute experiment, male S-D rats were given 0, 1, 2, 4, or 8 g DCE/kg in corn oil by gavage for 1, 5, or 10 consecutive days. The animals were housed in metabolism cages for collection of urine and sacrificed for blood and tissue sampling 24 h after their last dose. There were decreases in body weight gain and relative liver weight at all dosage levels, as well as increased renal nonprotein sulfhydryl levels at 2 and 4 g/kg after 5 and 10 days. Elevated serum enzyme levels, histopathological changes, and abnormal urinalyses were not manifest. For the subchronic study, adult male S-D rats were gavaged with 0.5, 1, 2, or 4 g DCE/kg 5 times weekly for up to 13 weeks. Animals receiving 4 g/kg exhibited pronounced CNS depression, with more than one-half dying by week 11. The 2-g/kg rats exhibited moderate CNS depression. One 2-g/kg rat died during week 6. There were very few manifestations of organ damage in animals that succumbed or in survivors at any dosage level. Decreases in bw gain and transient increases in enzymuria were noted at 2 and 4 g/kg. Serum enzyme levels and blood urea nitrogen were not elevated, nor were glycosuria or proteinuria present. Chemically induced histological changes were not seen in the liver, kidney, lung, brain, adrenal, spleen, stomach, epididymis, or testis. Hepatic microsomal cytochrome P450 experiments revealed that single, high oral doses of DCE did not alter total P450 levels, but did induce CYP2E1 levels and activity and inhibit CYP1A1 activity. These effects were reversible and regressed with repeated DCE exposure. There was no apparent progression of organ damage during the 13-week subchronic study, nor appearance of adverse effects not seen in the short-term exposures. One g/kg orally (po) was found to be the acute, subacute, and subchronic LOAEL for DCE, under the conditions of this investigation. In each instance, 0.5 g/kg was the NOAEL.

Acute, short-term, and subchronic oral toxicity of 1,1,1-trichloroethane in rats.

1,1,1-Trichloroethane (TRI) is a widely used solvent that has become a frequent contaminant of drinking water supplies in the U.S. There is very little information available on the potential for oral TRI to damage the liver or to alter its P450 metabolic capacity. Thus, a major objective of this investigation was to assess the acute, short-term, and subchronic hepatotoxicity of oral TRI. In the acute study, male Sprague-Dawley (S-D) rats were gavaged with 0, 0.5, 1, 2, or 4 g TRI/kg bw and killed 24 h later. No acute effects were apparent other than CNS depression. Other male S-D rats received 0, 0.5, 5, or 10 g TRI/kg po once daily for 5 consecutive days, rested for 2 days, and were dosed for 4 additional days. Groups of the animals were sacrificed for evaluation of hepatotoxicity 1, 5, and 12 days after initiation of the short-term experiment. This dosage regimen caused numerous fatalities at 5 and 10 g/kg, but no increases in serum enzymes or histopathological changes in the liver. For the subchronic study, male S-D rats were gavaged 5 times weekly with 0, 0.5, 2.5, or 5.0 g TRI/kg for 50 days. The 0 and 0.5 g/kg groups were dosed for 13 weeks. A substantial number of rats receiving 2.5 and 5.0 g/kg died, apparently due to effects of repeated, protracted CNS depression. There was evidence of slight hepatocytotoxicity at 10 g/kg, but no progression of injury nor appearance of adverse effects were seen during acute or short-term exposure. Ingestion of 0.5 g/kg over 13 weeks did not cause apparent CNS depression, body or organ weight changes, clinical chemistry abnormalities, histopathological changes in the liver, or fatalities. Additional experiments did reveal that 0.5 g/kg and higher doses induced hepatic microsomal cytochrome P450IIE1 (CYP2E1) in a dose- and time-dependent manner. Induction of CYP2E1 activity occurred sooner, but was of shorter duration than CYP2B1/2 induction. CYP1A1 activity was not enhanced. In summary, 0.5 g/kg po was the acute, short-term, and subchronic NOAEL for TRI, for effects other than transient CYP2E1 induction, under the conditions of this investigation. Oral TRI appears to have very limited capacity to induce P450s or to cause liver injury in male S-D rats, even when administered repeatedly by gavage in near-lethal or lethal dosages under conditions intended to maximize hepatic effects.

Congenital Heart Surgery Nomenclature and Database Project: aortico-left ventricular tunnel.

The extant nomenclature for aortico-left ventricular tunnel is reviewed for the purpose of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. Efforts were made to include all relevant nomenclature categories using synonyms where appropriate. The Hovaguimian classification appears most useful to surgeons: type 1, a simple tunnel with a slit-like opening at the aortic end, no aortic valve distortion; type II, a large extracardiac aortic wall aneurysm of the tunnel with an oval opening at the aortic end, with or without ventricular distortion; type III, intracardiac aneurysm of the septal portion of the tunnel, with or without right ventricular outflow tract obstruction; and type IV, a combination of type II and III. A comprehensive database set is presented, which is based on a hierarchical scheme. Data are entered at various levels of complexity and detail, which can be determined by the clinician. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented which will allow for data sharing and would lend itself to basic interpretation of trends. Outcome tables relating diagnoses, procedures, and various risk factors are presented.

Congenital Heart Surgery Nomenclature and Database Project: diseases of the pericardium.

The extant nomenclature for pericardial disease is reviewed for the purpose of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. All efforts were made to include all relevant nomenclature categories, using synonyms where appropriate. No classification system has been reported. The groups were based on disease processes, and include: effusive pericarditis (pericardial effusion), constrictive pericarditis, cardiac tamponade, postoperative pericardial effusion, postoperative cardiac tamponade, postpericardiotomy syndrome, congenital defect, neoplastic process, benign mass, pericardial cyst, pneumopericardium, and chylopericardium. A comprehensive database set is presented that is based on a hierarchical scheme. Data are entered at various levels of complexity and detail, which can be determined by the clinician. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented that will allow for data sharing and would lend itself to basic interpretation of trends.

Congenital Heart Surgery Nomenclature and Database Project: cardiac tumors.

The extant nomenclature for cardiac tumors is reviewed for the purpose of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. All efforts were made to include all relevant nomenclature categories using synonyms where appropriate. Cardiac tumors are characterized as primary, tumors which arise directly from tissues of the heart, and secondary, tumors which arise from tissues distant from the heart, with subsequent spread to the otherwise normal tissues of the heart. Tumor types are noted in the hierarchical scheme. A comprehensive database set is presented which is based on a hierarchical scheme. Data are entered at various levels of complexity and detail which can be determined by the clinician. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented which will allow for data sharing and would lend itself to basic interpretation of trends.

Mechanical ventricular assistance: an economical and effective means of treating end-stage heart disease.

BACKGROUND: Heightened awareness of medical costs has escalated criticism toward expensive medical therapy. METHODS: The use of ventricular assistance devices (VADs) at Pennsylvania State University as a bridge to transplantation was reviewed. Records of 43 patients listed as status 1 from July 1991 to July 1994 were compared. RESULTS: This analysis demonstrated that for all patients treated with the intent to transplant, those who were bridged with a VAD exhibited a trend toward an improved transplantation rate (92% versus 68%) and a significantly greater rate of discharge from the hospital (92% versus 55.4%; p = 0.023) than the medically managed patients. Although overall charges and costs were higher in VAD-supported patients, this was related to significantly longer pretransplantation hospitalization. When normalized to daily costs and charges, this discrepancy in expenses was eliminated. CONCLUSIONS: The superior rate of discharge at equitable daily costs and charges for the VAD patients draws continued enthusiasm toward use of these devices as a bridge to transplantation. Furthermore, development of outpatient care for VAD-supported patients and continued advances in the use of these devices may further reduce the cost of managing these critically ill patients.

The LionHeart LVD-2000: a completely implanted left ventricular assist device for chronic circulatory support.

Management of patients with end-stage cardiac disease remains a vexing problem. Limitations in medical management and a fixed supply of donor organs for cardiac transplant have a continued impact on this growing population of patients. Mechanical circulatory support has proved very successful as a means of bridging patients to cardiac transplant when all medical options have been exhausted. The development of a chronic system of circulatory support has been underway at the Pennsylvania State University for nearly 30 years. These efforts have been recently merged with the industrial partnership with Arrow International toward the development of the LionHeart LVD-2000 (Arrow International, Reading, PA) completely implanted left ventricular support system. We present an overview of the system, details of implantation, a review of preclinical studies, and a synopsis of the first European implants. Early results have demonstrated the system to be safe, effective, and reliable. Transcutaneous energy transmission and the compliance chamber have been validated.

Results of mechanical ventricular assistance for the treatment of post cardiotomy cardiogenic shock.

The voluntary submission of data on patients who receive mechanical circulatory assistance for post cardiotomy cardiogenic shock and acute myocardial infarction has resulted in an established data base for the ongoing evaluation of these devices. Since its inception in 1985, there have been 1,279 cases reported of implanted ventricular assist devices for post cardiotomy cardiogenic shock. The average duration of support for these devices is approximately 4 days. Those patients who underwent implantation of a centrifugal pump had significantly shorter periods of support when compared with the pneumatically supported group. Patients had similar periods of support when comparing clinical outcome. Approximately 70% of the reported cases underwent centrifugal assistance. The majority of reported cases were supported with isolated left ventricular assistance. There was no significant difference in overall outcome statistics when comparing type or mode of support. Approximately 45% of reported patients were weaned from circulatory assistance, and 25% of all patients survived to discharge. These numbers remain consistent with previously reported statistics. The results with acute myocardial infarction remain limited. Of the 96 reported patients, 26% were weaned from support and only 11.5% survived to discharge. This report continues to support the use and research for advancement of these devices toward the treatment of post cardiotomy cardiogenic shock.

Testing of a 50 cc stroke volume completely implantable artificial heart: expanding chronic mechanical circulatory support to women, adolescents, and small stature men.

The development of a completely implanted total artificial heart at our institution has progressed to successful in vivo and in vitro testing of a device that is nearing clinical testing. This system consists of a 70 cc stroke volume pump originally designed to be used in men of average stature. Implantation of this system remains limited by patient size; hence, many women and adolescent patients will likely be precluded from support because of their smaller stature. A system similar in design, but with a 50 cc stroke volume pump has been developed. The first in vivo study of this device has been undertaken. A calf was supported for 33 days. The animal was extubated and ambulatory within the first 6 hours of implantation, and remained healthy until the thirty-third postoperative day when it suffered an embolic neurologic event. The pump and operating system worked flawlessly throughout the period of support. Further in vivo and in vitro testing will be undertaken. Development of a scaled down total artificial heart system expands this type of circulatory support to those critically ill patients previously deemed poor candidates because of their smaller body habitus.

Bridging to transplant. Equal extended survival for patients undergoing LVAD support when compared with long-term medical management.

Implantation of ventricular assist devices (VADs) to support patients awaiting cardiac transplant has become an effective means of assuring that these critically ill patients survive to transplant. The authors undertook a retrospective analysis of 115 consecutive patients listed for cardiac transplant from January 1992 through June 1995. A VAD was implanted in 19 of these patients. Survival was calculated by intent to treat from the time of transplant listing through heart transplant, if it occurred. The analysis demonstrates that the patients who underwent implantation of a VAD as bridge to transplant had survival times similar to those of patients with medical management. These survival statistics demonstrate the utility of VADs as an effective means to bridge critically ill patients until a suitable donor organ becomes available. In addition, as previous studies have suggested for acute results, earlier implementation and better patient selection may lead to improved long-term survival.

Performance of low-pressure cuffs. An experimental evaluation.

A study was carried out in vitro to determine the minimum intracuff pressure needed to produce no-leak ventilation and prevent aspiration in Portex Profile and Searle Medical Sensiv endotracheal tubes. The mean pressures required to produced no-leak ventilation were 4.16 and 1.06 kPa respectively and the mean pressures at which aspiration occurred were 2.93 and 0.54 kPa respectively. The implications of these findings are discussed and recommendations are made regarding cuff specifications.

Reporting of instrument validity and reliability in selected clinical nursing journals, 1989.

Before research findings are applied to practice, the quality of the research must be assessed so that flawed research does not lead inadvertently to flawed practice. Two critical indicators of research quality are the validity and reliability of the data collection instruments. This article summarizes the principles of instrument validity and reliability and identifies deviations from these principles in a random sample of 55 research studies published in 1989 in five refereed nursing journals targeted toward practicing clinicians. Using a valid and reliable instrument, the investigators found that even with a policy of giving authors "the benefit of the doubt," 47% of the research studies contained no evidence of validity for any data collection instruments and 36% had no evidence of reliability; 29% had no evidence of either validity or reliability. Content validity, a basic requirement for all research instruments, was addressed in only 27% of the studies. This article provides documentation, justification, and suggestions for nursing educators, journal editors, and researchers to take action to improve the reporting of instrument validity and reliability to help ensure the quality of the research on which nursing practice is based.

Effects of ranitidine on the enzyme cholinesterase and the rat anococcygeus muscle.

Ranitidine in lower doses, (100 ng and 1 microgram) accelerated the rate of reaction of the enzyme acetylcholinesterase with the substrate acetylthiocholine. However, in higher doses (10 micrograms and 100 micrograms) it inhibited the enzyme activity. In rat anococcygeus muscle preparation, the responses to acetylcholine were significantly inhibited in lower doses whereas in higher doses there was a dose-dependent potentiation of the responses to acetylcholine by ranitidine. The responses to carbachol were however, not affected by ranitidine in the same preparation. Our data suggest cholinomimetic as well as cholinolytic activity of ranitidine.