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Biomedical subjects

P R Lynch

Publications and source records attributed to P R Lynch.

At least 19 recordsLinked to original sources

The effects of nicotinamide and hyperbaric oxygen on skin flap survival.

Hyperbaric oxygen has been established as an acceptable treatment for the chronic healing wound. Nicotinamide has been shown to be angiogenic and accelerate the physiologic process following wounding. Therefore both nicotinamide and hyperbaric oxygen were evaluated to enhance flap survival in an island pedicle skin flap model. These two treatment modalities were evaluated alone and in combination to assess if there is an addictive effect to enhance flap survival. Forty Sprague-Dawley male rats (weight 300-350 grams) were treated for 14 days preoperatively 1 day post-operatively with either 400 mg of nicotinamide i.p. or saline i.p. On day 14, a 7 X 7 cm island pedicle skin flap was elevated ligating the left inferior epigastric neurovascular pedicle and were sutured in their normal position. Twenty animals then underwent hyperbaric oxygen treatments. Forty-eight hours post-operatively animals were re-anesthetized and were given a single injection of fluorescein (25 mg/kg) via the tail vein. The % survival of the flap and SEM of the groups are as follows: Saline 45.67 +/- 31.14, nicotinamide 85.30 +/- 9.24, saline-hyperbaric oxygen 76.70 +/- 9.42 and nicotinamide-hyperbaric oxygen 90.86 +/- 3.94 with statistical significance of p less than 0.01. Nicotinamide appears to be another acceptable therapeutic modality in the management of the acceleration of wound healing.

Animals

Effects of intravenous perfluorocarbon and oxygen breathing on acute decompression sickness in the hamster.

Anesthetized female hamsters (Mesocricetus auratus) were divided into 3 experimental groups with 16 animals in each group. After control arterial blood pressure and ECG recordings, the animals were placed in a hyperbaric chamber for 30 min at 7 ATA and then decompressed directly to the surface at a rate of 60 fsw/min. After their removal from the chamber, animals were either not treated (group 1); given i.v. saline while breathing 100% oxygen (group 2), or given i.v. oxypherolperfluorochemical (Fluosol-43) perfusion emulsion while breathing 100% oxygen (group 3). Thirty minutes after decompression, all but one of group 1 had died (a 6% survival rate). Group 2 had a 62% survival rate and group 3 had a 94% survival rate. Perfluorochemicals were observed to reduce the number of bubbles formed, enhance bubble disappearance, and reduce dysrhythmias.

Animals

Biplane ventriculography in the rat.

Biplane ventriculography was performed on nine intact anesthetized rats. Images of the left ventricle large enough for analysis were obtained by placing the rats close to the radiographic tubes (direct enlargement). Sampling rates, adequate for heart rates of 500 beats/min, were obtained by filming at 500 frames/s. From the digitized silhouettes of the left ventricle the following information was obtained (means +/- SE): end-diastolic volume 0.60 +/- 0.03 ml, end-systolic volume 0.22 +/- 0.02 ml, stroke volume 0.38 +/- 0.02 ml, ejection fraction 0.63 +/- 0.02, cardiac output 118 +/- 7 ml/min, diastolic septolateral dimension 0.41 +/- 0.01 mm, diastolic anteroposterior dimension 0.40 +/- 0.01 mm, diastolic base-to-apex dimension 1.58 +/- 0.04 mm. To determine the accuracy with which the volume of the ventricle could be measured, 11 methyl methacrylate casts of the left ventricle were made. The correlation was high (r = 0.99 +/- 0.02 ml E) between the cast volumes determined by water displacement and by use of two monoplane methods (Simpson's rule of integration and the area-length method applied to the analysis of the anteroposterior films) and a biplane method (area-length). These results demonstrate that it is possible to obtain accurate dimensions and volumes of the rat left ventricle by use of high-speed ventriculography.

Animals

Impedance cardiography. Current status and clinical applications.

Impedance cardiography is a highly reproducible, rapid and safe method for the evaluation of cardiac performance in the clinical setting. Measurements of stroke volume (SV), end diastolic volume (EDV), and end systolic volume (ESV) with calculation of cardiac output (CO) were obtained in normal, healthy people (group 1, n = 21) and in patients with congestive heart failure (group 2, n = 18). Individuals were placed on a tilt table and cardiac profiles (measurements of CO, SV, EDV, and ESV) were performed at 45 degrees head up, 15 degrees head up, and supine. Group 1 responded by increasing CI from 2.9 +/- 0.81 L/min/M2 at 45 degrees to 3.3 +/- 1.0 L/min/M2 at 15 degrees to 3.7 +/- 1.0 L/min/M2 supine. There was no corresponding rise seen in group 2, with CIs of 2.1 +/- 0.83 L/min/M2, 2.0 +/- 0.78 L/min/M2 and 2.0 +/- 0.76 L/min/M2 at each position, respectively. In addition, while the EDV increased at each position in group 1 (45 degrees: 71 +/- 21 cc/M2, 15 degrees: 88 +/- 26 cc/M2, Supine: 102 +/- 29 cc/M2), no such increase was evident in group 2 (45 degrees: 57 +/- 29 cc/M2, 15 degrees: 52 +/- 20 cc/M2, Supine: 60 +/- 24 cc/M2). The inability of group 2 patients to elevate CI and the absence of any discernible change in EDV suggests an insufficiency of cardiac reserve with noncompliant ventricles. This information is currently being used to assess operative risk and to study effects of treatment modalities.

Cardiac Output

Radioprotection of the kidney with degradable microspheres. A pilot study in the dog with repeated irradiation.

The left kidney of 9 dogs was irradiated daily for three days with 300 kVp X-rays. Radioprotection was attempted in 5 of the kidneys by administration of degradable microspheres in the renal artery, immediately before irradiation. Protected kidneys received 3 X 8 or 3 X 12 Gy in midplane dose, unprotected kidneys 3 X 5.2 or 3 X 8 Gy. A protective effect due to induced hypoxia could be demonstrated in creatinine clearance, which was significantly higher in protected than in unprotected kidneys at 7 - 13 weeks after irradiation.

Animals

Origin and time course of gas bubbles following rapid decompression in the hamster.

Because conflicting results have been obtained in studies of the hamster (Mesocricetus auratus) microcirculation following rapid decompression, we were interested in the origin of bubbles in the cheek-pouch preparation. The hamster cheek-pouch and surgically exposed femoral vessels were observed under the microscope, before and immediately following rapid decompression. The animals were placed in a hyperbaric chamber and exposed to an increased pressure of 7 ATA for 1 h. They were then decompressed at a rate of 18 m/min until reaching 1 ATA. This hyperbaric exposure produced an LD50 in 100 hamsters examined in this study. In 40% of these animals "bubbles" were seen entering the cheek-pouch artery after a delay of from 3 to 6 min following decompression. Before observing bubbles in the cheek-pouch artery, bubbles were always seen in the femoral vein. Those animals that had observable bubbles in the cheek-pouch usually demonstrated a tachypnea, followed by gasping and apnea. When bubbles were seen in the arterial circulation, few animals survived for more than 10 min following the hyperbaric exposure. Postmortem examination of these animals revealed massive gas emboli in the large venous vessels, right ventricle, and fewer bubbles in the left ventricle. Postmortem examination of surviving animals revealed that the majority of the gas was in the venous vessels and right heart. These data support the hypothesis that bubbles first form on the venous side of the circulation and, if they exceed a certain volume, move through the pulmonary circulation into the systemic arterial vessels.

Animals

Effects of ioxaglic acid on cardiac functions during coronary arteriography in canines.

The new monoacid dimer ioxaglic acid (P286), The non-ionic metrizamide (Amipaque) and diatrizoate (Renografin 76) were compared regarding their effects on left ventricular pressure, the first derivative of left ventricular pressure, aortic pressures and on ECG changes during left and right coronary angiography in dogs. Ioxaglate was found to affect most of these parameters less than diatrizoate probably due to its lower osmolality. Ioxaglate should be regarded suitable for coronary angiography. However, ioxaglate was found to have greater effects on the cardiac function than the equiosmolar metrizamide. This is probably due to the chemotoxicity of the anion or possibly to the sodium content of the ioxaglic acid solution.

Angiography

Decompression incidence in air- and liquid-breathing hamsters.

The effects of hyperbaric compression on heart rate, rectal temperature, respiratory rate, bubble formation, and survival were studied in three groups of anesthetized golden hamsters (Mesocricetus auratus). Group I (15 animals) breathed air while exposed to 7 ATA of pressure for 1 h in a hyperbaric chamber; Group II (13 animals), at the same pressure level (7 ATA) and for the same time period (1 h), breathed an oxygenated fluorocarbon liquid (temperature 27 degrees C) that was open to the chamber atmosphere; Group III (10 animals), at the same pressure and time period as the other groups, were sealed in a flexible plastic bag filled with oxygenated fluorocarbon as a breathing mixture. A fourth, Group IV (12 animals), breathed oxygenated fluorocarbon for 1 h at 1 ATA. Survival after rapid decompression in each group varied, 9 animals died in Group I, 12 animals in Group II, whereas none of the animals died in either Groups III or IV. Thirty minutes after decompression postmortem examinations of all the animals demonstrated the presence of large amounts of gas bubbles in the right ventricle and some gas bubbles in the left ventricle of all the hamsters in Groups I and II. No gas bubbles were found in the hearts of the Group III animals. Group III animals, breathing a liquid unsaturated by an inert gas, survived rapid explosive decompression without the signs and symptoms of decompression sickness. Immersion in the liquid fluorocarbon produced a profound decrease in heart rate, rectal temperature, and respiration in Groups II, III, and IV.

Air

Frequency analysis approach to the origin of the first and second heart sounds.

Catheter-tipped micromanometers were used to simultaneously record left ventricular and aortic pressures, and left ventricular and aortic internal phonocardiograms in order to determine if they had a common mode of origin and propagation. Spectrographic analysis showed that even with high-pass filtration the phonocardiogram obtained with a commonly used system (Millar) contained large amounts of energy in the subaudible frequency range (below 40 Hz). It was possible to derive close facsimiles of the phonocardiograms by double differentiation of the corresponding pressure pulse and conversely to derive the pressure pulse by double integration of the phonocardiograms. The propagation velocities of the first heart sound, second heart sound, and the foot of the aortic pressure pulse were found to be similar and were respectively, 4.3 +/- 0.2, 4.6 +/- 0.3, and 4.2 +/- 0.2 m/sec (+/- SE). These data support the concept that the low frequency pressure variations produced by the heart, which predominate in the left ventricular and aortic pressure pulse waveforms, are generated and propagated in the same manner as the high frequency pressure variations, which are the first and second heart sounds.

Animals

Relationship between stroke volume and pneumocardiogram.

The intratracheal pressure oscillations produced by the heartbeat, called the pneumocardiogram, were recorded in 15 dogs. It was found that a linear relationship existed between the amplitude of the major negative deflection of the pneumocardiogram and the cardiac stroke volume, the latter determined either by indicator dilution (avg r = 0.94) or by use of an electromagnetic flow probe (avg r = 0.95). This relationship existed in animals with both an open and a closed chest. The vector of left ventricular wall motion directed toward the lungs, determined by high-speed cineradiography of the motion of a tantalum marker inserted in the wall of the left ventricle, looked very similar to the pneumocardiogram. This study showed that the pneumocardiogram can be used as a noninvasive technique to measure changes in stroke volume and is caused primarily by the motion of the cardiac walls.

Animals

Measuring pulmonary vascular congestion with quantitative radiographic indexes from digitized images.

Experiments were conducted with the aim of deriving quantitative indexes from radiographs that describe the status of the pulmonary vasculature under hypervolemic doncitions. Hypervolemia was induced in four baboons by the infusion of dextran solution. Left ventricular pressures were monitored in the erect animals during the infusion and radiographs were obtained. The radiographs subsequently were digitized with a scanning laser-densitometer and a PDP 11/40 minicomputer. An index was derived (the vascular complexity index, Cx), which combined the mean density difference between upper and lower lung zones (indicative of incipient pulmonary edema) and the ratio of density variations in the upper versus lower zones (indicative of redistribution of blood flow). The data indicate a good correlation between left ventricular and diastolic pressure and Cx during the infusion in each animal.

Animals

Blood and blood vessel wall changes induced by decompression sickness in dogs.

Healthy female dogs of mixed breed were anesthetized with pentobarbital sodium and given 51Cr-labeled autologous red blood cells and 125I-labeled anticanine vessel wall fiber (collagen and elastin) antibody. The anesthetized dogs were exposed to the equivalent of a 220-ft dive on air for 40-45 min (descent rate 75 ft/min, ascent rate 60 ft/min). The animal's condition was adjusted by additional shorter and/or shallower dives. Four dogs had mild decompression sickness (DCS), and seven had severe DCS judged by electrocardiogram. Three of the seven died before completion of the experiment. Permeability of the endothelial sheet of jugular veins and carotid arteries to the tracer (125I-gamma-globulin) was significantly increased in animals with severe but not mild DCS. There was slight hemoconcentration (increased capillary and venular permeability). Scanning electron microscopy showed that the endothelium was grossly intact with no evidence of mechanical damage, but giant cells (derived from monocytes) frequently adhered to the endothelium. Leukocytes and platelets adhered occasionally. Fibrin monomer was found in the plasma. Thus DCS is accompanied by endothelial cell alteration and limited blood cell adhesion to vessel walls in addition to activation od the clotting mechanism.

Animals

Contractile function in canine right ventricle.

Regional right ventricular (RV) motion was examined in six acutely instrumented dogs by implanting radiopaque markers in three regions of the free wall: the apex, the midventricle, and the outflow tract. These markers were filmed at the paced heart rate of 180 beats/min with a high-speed biplane X-ray system, and their motion was analyzed with a digital computer. Local deformation was separated into percent length changes in the two mutually perpendicular principal directions. The major component exhibited shortening along a path from apex to conus. (apex - 13.6%, midventricle -13.1%, conus -8.7%); the minor component exhibited small amounts of lengthening and some shortening (apex +4.7%, midventricle +1.8%, conus -0.5%). From these two measurements we calculated the peak RV free wall thickening (apex 13.6%, midventricle 14.1%, conus 10.9%). The experimental technique developed for this study was found to be suitable for the repeated analysis of intact ventricular performance in chronic animal studies. The results reveal that in systole the RV free wall undergoes a sequential contraction, which begins at the apex and ends in the conus.

Animals

The response of canine veins to three types of abdominal surgery: a scanning and transmission electron microscopic study.

Several studies have suggested that events which initiate deep venous thrombosis (DVT) occur in the early postoperative or interoperative period. Since DVT is a complication of many surgical procedures, an understanding of the early events which initiate DVT would be highly desirable. We have studied these events in a canine surgical model. The early response of the endothelium and the adhesion of blood elements to the luminal surface of veins was compared following three types of surgical trauma. Sixteen dogs were divided into four groups (control, splenectomy, hysterectomy, intestinal anastomoses) of four animals each. Blood was removed by perfusion 4 hours after anesthesia alone (control dogs) or anesthesia and surgery (experimental dogs). Jugular veins were removed for scanning and transmission electron microscopy. Veins from control dogs were covered by a continuous sheet of endothelial cells with some pseudopod formation and minor deposition and adhesion of cellular and noncellular material on the luminal surface. The response of veins from experimental animals varied considerably in the three types of surgery studied. The least-affected veins were those from splenectomized animals. These veins had patchy areas of cellular and noncellular material (10 veins) and occasional microthrombi deposited on the luminal surface (one vein). The veins from dogs subjected to hysterectomy exhibited greater endothelial alteration, including crater formation (two veins) and more cellular adhesion, particularly erythrocytes (eight veins). The veins from intestinal anastomoses animals exhibited the greatest response. In these animals there was considerable cellular and noncellular material deposited on the luminal surface of six veins from three of the four animals. The cellular material consisted primarily of erythrocytes and leukocytes, and the noncellular material was an amorphous granular substance. The other two veins were similar in appearance to the control veins. These findings would support the concept that deep venous thrombosis can begin in the interoperative or early postoperative period and that therapeutic intervention in the preoperative and interoperative periods might help prevent subsequent DVT.

Abdomen

Intravascular electrically induced thrombosis in the dog. Thrombus detection by ionic and nonionic contrast media.

Reliable, large, nonobstructive thrombi were produced by electrical stimulation of the wall of the inferior caval veins in dogs, thus avoiding surgical trauma or introduction of chemical substances. Metrizamide was found to adhere longer to the thrombi than an ionic medium (iothalamate) at comparable iodine concentrations. This may be due to the much higher viscosity of metrizamide.

Animals