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Biomedical subjects

R E Clark

Publications and source records attributed to R E Clark.

At least 253 records · Page 14Linked to original sources
PubMed1983

Nifedipine cardioplegia experience: results of a 3-year cooperative clinical study.

Previous animal studies and a preliminary clinical trial of the addition of nifedipine to cardioplegic solution demonstrated salutary effects in terms of postischemic performance. This report examines the combined results of extended clinical trials conducted in two centers: Barnes Hospital, St. Louis, and Allegheny General Hospital, Pittsburgh. From an open-heart population of 4,777 patients, 205 highest-risk persons were selected for study. One hundred seventy of them were given nifedipine in cardioplegic solution. The remaining 35 served as controls to compare with 39 treated patients in the randomized subset of 74. Thirty-eight percent were women; the average age was 61 +/- 1 year; and most were in New York Heart Association Class IV. One-third had valve replacement, one-quarter had coronary artery bypass grafting (CABG), and 37% had valve, CABG, and other procedures in combination. Characteristically, these patients had a 50% increase in end-diastolic volumes, low cardiac indexes (1.7 +/- 1 L/min/m2), and low left ventricular stroke work indexes (22 +/- 2 gm-m/m2). Average cross-clamp time was 77 minutes. At Allegheny, an extracellular hyperkalemic solution was used to deliver an average dose of 407 +/- 22 micrograms per patient. At Barnes, a low-sodium hyperkalemic solution was used; the average dose was 476 +/- 22 micrograms. The results of hemodynamic studies in the randomized subset demonstrated approximately a twofold greater improvement in the treated group in cardiac index, stroke volume, left ventricular stroke work index, and pulmonary vascular resistance immediately after bypass. The incidence of acute low cardiac output death was 4% versus 11% in the nontreated group. The hospital survivorship for all treated patients was 84%. It is concluded that the addition of a calcium antagonist, nifedipine, reduced the incidence of acute global cardiac failure in the immediate postoperative interval.

Aged↗
PubMed1983

Determination of the accuracy of laminated wax interocclusal wafers.

The variables that were selected as relevant factors in the production of inaccuracy in laminated wax interocclusal wafers were found to be highly significant statistically, mostly with confidence levels greater than 99%. These confidence levels, however, relate to experimental comparisons in the absence of any absolute standard. Clinical impact is difficult to assess without such standards. Laminated wax interocclusal wafers are highly technique sensitive. Variations in treatment and handling procedures are important factors in assessing their accuracy. Wafers that were both laminated and metalized were found to be the most accurate and dimensionally stable. However, exact reproductions of the original wax recordings are unlikely and were not achieved in this investigation.

Evaluation Studies as Topic↗
PubMed1982

The clinical life history of explanted prosthetic heart valves.

This report analyzes 118 prosthetic heart valves obtained from 97 patients at reoperation (96) or at postmortem examination (22). The number obtained from the mitral, aortic, and tricuspid positions were 78, 32, and 8, respectively. Duration of implant ranged from one day to 12.3 years. Valves showing the least long-term wear were the Starr-Edwards metal strut-silicone bell and the Björk-Shiley. Moderate long-term durability was provided by the Beall and Starr-Edwards cloth-covered composite-seat prostheses while short-term durability was given by Hancock and Carpentier valves. Reoperation for valve-related causes was performed for 46 of 47 Beall valves, which demonstrated stenosis, hemolysis, and incompetence from component wear, 6 of 27 Björk-Shiley prostheses for valve thrombosis or thromboembolism or both, and 11 of 17 porcine prostheses because of calcification (4) or cusp perforation or rupture. Analyses of wear and fatigue of mechanical valves demonstrated that use of ultrahard materials (pyrolyte carbon, titanium, stellite 21) provided superior durability in contrast to polymeric solids or fabrics with poor abrasion and impact characteristics. Further, cloth and disc wear were evident as early as 0.5 year after implant and appeared to be complete by 4 years. Completeness of healing after 24 months was not related to the type of fabric material used or its construction. This study suggests that mechanical valves made from hard materials have long durability when properly implanted and require fastidious prophylaxis against infection and thromboembolism. The findings of early cusp perforation or rupture in the aortic position and leaflet calcification, stiffening, or disruption in the mitral position for porcine prostheses suggest that frequent and careful examinations of patients with these prostheses are required to detect early signs of stenosis or incompetence and that early reoperation is required before catastrophic valve failure necessitates emergency prosthetic valve replacement.

Aortic Valve↗
PubMed1982

Production and characterization of monoclonal antibodies to rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

Rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase [HMG-CoA reductase; mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34], the key regulatory enzyme in cholesterol biosynthesis, has been purified to apparent homogeneity. Purified HMG-CoA reductase yields a single diffuse band when NaDodSO4/polyacrylamide gels are stained with Coomassie blue and yields two adjacent bands when gels are stained with silver. Purified reductase was used to elicit the production of monoclonal antibodies. Spleen cells from BALB/c mice immunized with purified HMG-CoA reductase were fused with Sp-2/0 myeloma cells. Clones producing monoclonal antibodies to HMG-CoA reductase were identified by using a solid-phase radioimmunoassay and were subcloned in soft agar. The three relatively stable hybridoma lines isolated secrete different Igs as judged by their antibody subclasses and differing abilities to inhibit HMG-CoA reductase in solution. Efficient precipitation of solubilized HMG-CoA reductase was achieved with the two IgG antibodies but not with the IgM. A mixture of all three monoclonal antibodies immunoprecipitates more than 90% of the HMG-CoA reductase activity in solubilized rat liver extracts. These monoclonal antibodies should be useful probes for investigation of the regulation of HMG-CoA reductase and cholesterol synthesis.

Animals↗
PubMed1982

Adequacy of the perfusate: its influence on successful myocardial protection.

The hypothesis tested was that the composition of the prime and the perfusate at the time of reperfusion had an influence on postischemic cardiac performance. Twelve dogs in two equal groups had long (210 +/- 10 minutes) hypothermic (25 degrees +/- 1 degree C) perfusions. Each had 180 minutes of global ischemia and were given 500 ml of the same cold (4 degrees C) cardioplegic solution (CPS) every 45 minutes and topical hypothermia with a resultant average myocardial temperature of 10 degrees +/- 2 degrees C. Group A had a prime (1,958 ml) consisting of a 50/50 mixture of 5% dextrose in water and 5% dextrose in Ringer's injection to which mannitol (12.5 gm), furosemide (20 mg), and heparin (6,000 units) were added. Group B received a prime (1,868 ml) of 5% dextrose in Ringer's injection (1 L) and 750 ml of 6% helastarch in normal saline to which NaHCO3 (10 mEq), furosemide (20 mg), mannitol (25 gm), and heparin (6,000 units) were added. During perfusion, Group A received lactated Ringer's solution and Group B received a 1 : 2 portions of Ringer's injection and 6% helastarch. Additionally, Group B received additional furosemide and mannitol 5 minutes prior to the reperfusion interval. The results showed a marked difference between groups in postischemic cardiac recovery 120 minutes after cessation of cardiopulmonary bypass. The Group B dogs had statistically (less than 0.02) greater cardiac output, stroke volumes, and stroke work index at equal preloads and lower total peripheral resistances. Arterial systolic, diastolic, and mean pressures and right atrial pressures were not different. The Group A dogs required nearly threefold the volume of fluid additions required during bypass and twice the amount of NaHCO3 as Group B dogs. It is concluded that the composition of the prime and fluids used during bypass and use of agents to counteract tissue water accumulation during the ischemic and reperfusion intervals strongly influences postischemic cardiac performance. Further, these data suggest that the composition of the perfusate may have a greater influence on the functional recovery of the heart than the composition of various CPSs.

Animals↗
PubMed1981

The effect of immediate dentures on maxillomandibular relations.

Immediate mandibular and maxillary dentures were made for six patients to determine the relative changes in the vertical dimension of occlusion and rest position over a 3-month test period. The dentures were mounted on the articular in centric occlusion (habitual). Pilkington-Turner anatomic teeth were used on the maxillary denture, which was set against a flat, noninterfering acrylic resin occlusion rim instead of mandibular posterior teeth. Positional cephalometric measurements in centric occlusion and rest position were made before extraction and at 1-week, 1-month, 2-month, and 3-month intervals. The dentures were relined after 2 months. The results were as follows: 1. In the centric occlusion position the mandible moved forward after 1 week and remained forward for the 3-month test period. 2. The rest position showed no significant change in the anteroposterior position of the mandible with time. 3. The vertical dimension of occlusion and rest showed a gradual decrease over the entire test period. 4. The reline procedure did not affect the trend of the dimensional changes. 5. A noninterfering occlusal scheme is advantageous for immediate dentures.

Adult↗
PubMed1981

Myocardial preservation with nifedipine: a comparative study at normothermia.

Sixty-four dogs were placed on normothermic total cardiopulmonary bypass, and global ischemia was induced for 1 hour during which continuous infusions (240 ml per hour) (N = 39) or bolus injections (150 to 200 ml every 30 minutes) (N = 23) into the proximal aortic root were performed. The control groups (N = 26) had infusion or injection of normal saline solution, normal saline solution + 25 mEq/L of potassium chloride, or Normosol-R pH 7.4. The cardioplegic solution (N = 15) contained 25 mEq/L of potassium chloride in Normosol-R pH 7.4, 0.25 mg/ml of lidocaine, 500 mg/dl of glucose, and 1.8 microU/ml of insulin. The nifedipine group (N = 23) had infusion or injection of 0.167 to 0.2 microgram/ml of nifedipine in saline solution, Normosol-R pH 7.4, or the cardioplegic solution. Left ventricular performance was assessed by phasic and mean measurements of left ventricular peak and end-diastolic pressures and its first derivative, left and right atrial pressures, and ascending aortic blood flow. Calculations of stroke work index and total peripheral resistance were performed. Morphological examinations, and light and electron microscopic examinations of heart slices were done. The results demonstrated a consistent superiority of the nifedipine group in terms of performance after bypass compared with the cardioplegic or control group. Normal preischemic stroke work indices and Sarnoff curves were present 2 hours after bypass for the nifedipine-treated groups. The cardioplegic solution was ineffective when given continuously but gave modest protection when given as a bolus injection. It is concluded that the concept of the efficacy of calcium blockade during ischemia and the initial reperfusion period for enhanced myocardial protection is valid.

Animals↗
PubMed1981

Laboratory and initial clinical studies of nifedipine, a calcium antagonist for improved myocardial preservation.

This report summarizes five years of laboratory investigations and the initial six-month clinical experience with a calcium antagonist, nifedipine, added to a cold hyperkalemic cardioplegic solution for enhancement of myocardial protection. Regional ischemia was created in 112 dogs and global ischemia in 98 dogs, under normothermic and two hyperthermic states. Control solutions, two clinical cardioplegic solutions, and nifedipine solutions were compared. Infusion of nifedipine during regional ischemia and reperfusion intervals resulted in a two-to-threefold reduction in injury volume and maintenance of normal left ventricular function in contrast infusion of nitroprusside. Nifedipine solutions (0.2 microgram/ml) provided superior preservation of left ventricular function in comparison to the two cardioplegic solutions after one hour of global ischemia at 37 degrees C and two hours at 18 C. In a clinical trial of nifedipine in cold potassium cardioplegia, 38 high risk patients with poor ventricular function have been treated; 22 of which were intensively studied serially with radionuclide ventriculography and pyrophosphate scans, myocardial isoenzyme determinations, 24 hour EKG recordings and intra- and postoperative hemodynamic studies. Of the 35 patients admitted to the intensive care unit (ICU), 33 have survived. Stroke work and cardiac indices return promptly to near normal levels after operation. The time-isoenzyme activity curves are low and radionuclide determined ejection fractions show no change for the study group. Death from acute postischemic cardiac failure did not occur in treated patients and the usage of intra-aortic balloon pump (IABP) has decreased threefold in comparison with 40 similar high risk patients treated concurrently with cardioplegic solution alone. It is concluded that nifedipine is a potent adjunct to cold hyperkalemic cardioplegic solution in high risk patients.

Adult↗
PubMed1981

Chest film diagnosis of disc embolization in patients with Beall mitral valve prostheses.

This report presents the chest film findings in three patients with Beall mitral valve prostheses in whom severe disc wear resulted in disc embolization. In all three cases the worn disc embolized to the thoracic aorta with catastrophic decompensation, and all three patients were salvaged with emergency operation. Detection of the embolized disc was possible with plain chest radiography in each case and may permit removal of the embolized disc at the time of valve replacement. Early detection of disc wear and replacement of worn Beall mitral valve prostheses are advocated to avoid this left-threatening complication.

Aorta, Thoracic↗
PubMed1981

Three-hour preservation of the hypothermic globally ischemic heart with nifedipine.

We have previously shown that an intracellular-like crystalloid cardioplegic solution (ICS) provides superior protection to normothermic canine hearts subjected to 1 hour of global ischemia (GI) in comparison to a standard extracellular-type clinical cardioplegic solution (CPS). The addition of a calcium antagonist, nifedipine (N), to CPS was shown to be salutory. The new experiments used systemic hypothermia (25 degrees +/- 1 degrees C) and multidose (500 ml) cold (4 degrees C) CPS or ICS with and without N (200 to 400 micrograms/L) every 30 to 45 minutes during GI intervals of 3 hours at a resultant myocardial temperature of 10 degrees +/- 2 degrees C. The results show that after 3 hours of GI and 2 hours of observation stroke work index, (SWI) decreased to 50% +/- 10% of control for the CPS, ICS, and CPS + N groups. The ICS + N group had excellent preservation with left ventricular (LV) SWI and first derivatived left ventricular pressure (LV dP/dt) equal to the preischemic valve. Cardiac output was increased above control levels and responded normally to volume loading. Possible mechanisms of nifedipine and CPS interactions are discussed. It is concluded that a low sodium ICS containing N is highly efficacious for long ischemic intervals and that composition of the CPS strongly influences the effects of N on postischemic performance.

Animals↗
PubMed1980

An intracellular-like cardioplegic solution. Its enhancement of myocardial protection.

We sought to determine the relative protective effects of an intracellular-like, calcium-bearing, crystalloid solution (ICS) and a calcium-free, extracellular-like solution (ECS). Both solutions were similar in concentrations of potassium ions (25 to 26 mEq/L), in pH (7.7 to 7.8), and in osmolarity (340 to 360 mOsm/L). Normothermia was used to obviate masking the true effects of the solutions with the independent effects of hypothermia. Fifty-seven dogs were placed on cardiopulmonary bypass and had global myocardial ischemia for one hour. Continuous infusions and bolus injections into the aortic root of control solutions (n = 24), ECS (n = 15), and ICS (n = 16) were used. Two-hour postischemic ventricular performance was superior for ICS in comparison with ECS or control solutions regardless of administration mode. The multidose mode gave improved results with control and ECS groups. The use of an ICS yields improved postischemic performance in normothermic dog hearts.

Animals↗
PubMed1980

Experimental endocarditis in calf after tricuspid valve replacement.

A calf model for reproducible, prosthetic tricuspid valve endocarditis was developed using Staphylococcus aureus. The course of late prosthetic valve endocarditis was characterized as a fulminant disease when untreated with antibiotics. The earliest sign of a colonized valve prosthesis was an elevation of body temperature, which correlated with occurrence of positive blood cultures. The dose required to colonize an endothelialized tricuspid prosthetic valve in the calf model was 10(7) to 10(8) S. aureus organisms. In the model for late prosthetic valve endocarditis, silver-allantoin-heparin (SAH) treatment of the prosthetic valve gave no protection from inoculums of 10(8) S. aureus injected 60 days after operation. SAH treatment may be beneficial in early stages of prosthetic valve endocarditis, but this requires further study. Simultaneous cultures from the right atrium, the right ventricle, and the aorta of 2 animals showed that there was a 1,000- to 10,000-fold decrease in the bacterial titers across the combined pulmonary and systemic capillary beds. Bacterial titers drawn from the jugular vein had a 46% false negative result, and positive cultures from the external jugular vein showed only 1.3 S. aureus organisms per milliliter of blood. These bacteriological findings point out the risks of depending on sampling from the peripheral venous system when culturing for right heart endocarditis.

Allantoin↗