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Biomedical subjects

M P Kaye

Publications and source records attributed to M P Kaye.

At least 91 records · Page 5Linked to original sources

Hemodynamics of congenital diaphragmatic hernia in lambs.

Despite surgical treatment, congenital foramen of Bochdalek diaphragmatic hernia continues to carry a high mortality rate due to associated respiratory insufficiency. We studied the pathologic and hemodynamic changes that result from this condition in lambs. Surgical creation of diaphragmatic hernias in fetal lambs was performed in utero with subsequent delivery by cesarean section near term. Cardiac catheterization was performed on these newborn lambs immediately after delivery, before and after surgical repair of the defect. Data from five of these lambs were compared to data obtained from seven normal lambs. Pulmonary hypertension was found only in lambs with hernias. Pulmonary artery pressures and the mean ratio of pulmonary to systemic resistance were higher in experimental lambs. Oxygen saturation and average cardiac index were higher in normals. Lambs in the experimental group, but not in the control group, had large left-to-right shunts at the level of the ductus arteriosus in the early neonatal period. Arterial oxygen saturations were consistently low with no differences in pre- and post-ductal samples, which suggests right-to-left shunting at the atrial level or physiologic shunting across the unexpanded lungs. No further expansion of the hypoplastic lungs occurred following decompression by surgical hernia repair, but transient hemodynamic improvement was noted in some cases. Surgical ligation of the ductus arteriosus did not significantly alter the clinical condition of the lambs. Lungs in lambs with hernias were grossly abnormal, the left appearing more hypoplastic than the right.

Animals↗

Cardiac pacemakers in absence of the SA node: responses to exercise and autonomic blockade.

Surgical excision of the sinoatrial node, verified histologically, is followed by a supraventricular (atrial) rhythm in both resting and exercising dog whether anesthetized or conscious. The ECG is characterized by a definitive P wave and associated atrial electrograms. Waxing and waning in heart rate, generally referred to as sinus arrhythmia continues in the awake animal after complete excision of the SA node. This arrhythmia is responsive to both adrenergic and cholinergic interventions, thus indicating the presence of both sympathetic and parasympathetic regulation of subsidiary atrial pacemaking tissues.

Adrenergic beta-Antagonists↗

Norepinephrine uptake as an indicator of cardiac reinnervation in dogs.

To study the possible role of uptake of [3H]norepinephrine ([3H]NE) as an indicator of sympathetic reinnervation of the surgically denervated canine heart, uptake was determined from multiple areas of hearts at various stages of reinnervation (1--6 mo), and these data were correlated with myocardial catecholamine content and functional response of the heart to electrical stimulation of the sympathetic nerves. Our experiments confirm that NE content correlates poorly with the degree of reinnervation of the previously denervated canine heart. There is, however, a progressive increase of [3H]NE uptake from 1 mo to 6 mo, at which time uptake has returned to approximately 57% of control values in the left atrium. The development of the storage mechanism lags far behind the specific-membrane mechanism for uptake in the reinnervating surgically denervated canine heart.

Animals↗

Imaging platelet deposition with 111In-labeled platelets in coronary artery bypass grafts in dogs.

At 8 and 32 hours after saphenous vein aortocoronary artery bypass graft surgery in four dogs, images of the grafts were obtained with a gamma camera after intravenous injection, 2 hours postoperatively, of autologous platelets labeled with indium-111. The location of platelet deposition could be accurately estimated from the scintiphotos. In vitro radioactivity counting of the segments of the isolated grafts showed 4 to 15 times greater activity in the grafts than in blood and 25 to 100 times greater activity than in normal myocardium. This was sufficient for delineating accurately the area of platelet deposition. This noninvasive technique may be a promising tool for a better understanding of the role played by platelets in the process of occlusion of saphenous vein bypass grafts in man.

Animals↗

Myocardial ultrastructural changes after experimental ventricular fibrillation and anoxic arrest.

A transmural myocardial biopsy method was used to study changed in ultrastructure after induced ventricular fibrillation or anoxic arrest in the canine heart. Interstitial edema, mitochondrial derangement, contraction bands, and swelling of capillary endothelium were more extensive in subendocardial than in subepicardial layer after anoxic arrest. Significant numbers of contraction bands were also seen in the myocardium after induced ventricular fibrillation. These changes appeared to be reversible at least in part in the group with induced ventricular fibrillation but generally not in the anoxic arrest animals. After anoxic arrest, preservation of the endocardial layer was significantly poorer than that of the epicardium; after ventricular fibrillation, there appeared to be no such difference. Myocardial mitochondria and glycogen granules were intact and more numerous after ventricular fibrillation than after anoxic arrest. The lesser damage after ventricular fibrillation than after anoxic arrest suggest that the myocardium may be affected less by the no-reflow phenomenon after normal coronary circulation is restored in ventricular fibrillation.

Animals↗

Quantitative evaluation of myocardial ultrastructure following hypothermic anoxic arrest.

Thirty-six anesthetized mongrel dogs were subjected to systemic hypothermia and anoxic cardiac arrest while on cardiopulmonary bypass. Myocardial fine structure in the left ventricle was evaluated by quantitative analysis in the subepicardial, mid-myocardial, and subendocardial layers. The specimens were obtained by a transmural myocardial biopsy method. Graded hypothermia was employed at 36 degrees, 30 degrees, 28 degrees, 25 degrees, and 22 degrees C. The aorta was cross-clamped for 30 minutes at 36 degrees, 30 degrees, 28 degrees, and 25 degrees C. or for 45 minutes at 25 degrees and 22 degrees C. Observations indicated that pathological changes of the myocardial fine structure were significant after anoxic arrest in the normothermic group. Lesions were most extensive in the subendocardial layer after normothermic anoxic arrest, whereas hypothermia below 30 degrees C. preserved the myocardium throughout all layers without difference in pathological changes in the fine structure among the layers. Mitochondria and glycogen granules in the mid-myocardial layer and the subendocardial layer were best preserved with hypothermia at 25 degrees and 22 degrees C. after 30 minutes or 45 minutes of anoxic arrest, and dogs in these groups had a survival rate of 100 percent. Quantitative analysis of ultrastructural changes induced in these experiments suggest that a safe duration of anoxic arrest at 22 degrees to 25 degrees C. is between 30 and 45 minutes.

Animals↗

Chronology and mode of reinnervation of the surgically denervated canine heart: functional and chemical correlates.

This study was undertaken to evaluate functionally the time and pattern of inotropic and chronotropic efferent cardiac reinnervation of the deneravated canine heart and to correlate functional data with regional myocardial catecholamine content and supersensitivity to norepinephrine. Our data indicate that efferent autonomic reinnervation takes place first in the atria, followed by a base-to-apex sequence in the ventricles, and that such reinnervation is functionally effective 9-12 mo after denervation. The return of neural function parallels the return of measurable quantities of myocardial norepinephrine and is accompanied by a decrease in supersensitivity to exogenous norepinephrine. The return to apparently complete functional reinnervation, however, cannot be quantitatively related to myocardial levels of catecholamine. Segmental myocardial supersensitivity to norepinephrine is sequentially reversed during progressive adrenergic reinnervation.

Adrenergic Fibers↗

Radiographic assessment of leaflet motion of Gore-Tex laminate trileaflet valves and Hancock xenograft in tricuspid position of dogs.

Six samples of various thicknessess of Gore-Tex compounds were fashioned into trileaflet valves. A radiopaque marker was placed on the center of the free margin of each cusp, and the prostheses were implanted in the tricuspid position of dogs. Two Hancock valves were studied for comparison. Catheterization revealed that the hemodynamic function was normal in all valves tested. High-speed radiography permitted analysis of leaflet movement throughout the cardiac cycle. Of the six Gore-Tex valves, five opened completely. The cusps of these five valves were fabricated from 4, 6, 8, 10, and 12 layers of Gore-Tex film. The remaining valve, which was fabricated from 15 layers of Gore-Tex film, and both porcine xenograft aortic valves did not open completely. We postulate that the laminates of 12 layers or less of Gore-Tex film are suitable for further study to evaluate their potential applicability in trileaflet cardiac valve prostheses.

Animals↗

Function of expanded-polytetrafluoroethylene laminated trileaflet valves in animals.

A stent-mounted trileaflet cardiac valve prosthesis has been developed in which the valve leaflets were fabricated from 0.003-mm films of expanded polytetrafluoroethylene laminated in 4 to 15 layers. A total of 28 valves of varying leaflet thickness were implanted in the tricuspid position in dogs. Cardiac catheterization performed during the follow-up period between 1 week and 15 months after valve replacement in 20 surviving animals showed that the initial good function was maintained in 12 dogs for up to 15 months, whereas valve dysfunction developed in 8 other dogs within 6 months. Autopsy revealed that the cause of valve dysfunction among the eight dogs was cusp stiffening with or without retraction in six, dehiscence of the suture ring in one, and strut entrapment in one. This study demonstrated that the thickness of the leaflet material is an important factor affecting the long-term function in vivo.

Animals↗

[Selective ventricular and coronary denervation (author's transl)].

A technique for selective ventricular denervation is described and functional documentation of the effectiveness of this method is presented. Further evidence is presented to demonstrate that selective ventricular denervation interrupts the alpha-adrenergic coronary vasoconstriction fibers and significantly decreases the myocardial oxygen demands during sympathetic nerve stimulation.

Adrenergic Fibers↗

Cardiac dysrhythmias in the conscious dog after surgically induced autonomic imbalance.

The ventrolateral cardiac nerve in the dog is a primary branch of the left sympathetics and represents a direct neural link between the central nervous system and the heart. Its electric excitation elicits characteristic shifts in pacemaker and tachydysrhythmias related to its explicit innervation of the inferior atrial, atrioventricular (A-V) junctional and ventricular tissues. Total denervation of the canine heart, sparing the ventrolateral cardiac nerve, produced a long-term model in which only these portions of the heart retained their sympathetic innervation. The trained unanesthetized model dog was subjected to severe exercise in order to determine the effects of elevated levels of sympathetic tone upon these important regions of the conduction system. Reproducible tachydysrhythmias were elicited in all six animals completing the regimen of periodic testing over a period of 136 to 378 days after operation. The abnormal rhythms consisted of shifting cardiac pacemakers and supraventricular A-V junctional and ventricular tachycardias with frequent premature systoles. Comparable abnormalities were not observed in a similarly tested sham-operated animal or in dogs with a totally denervated heart. The exercise-induced dysrhythmias gradually disappeared with time, presumably in relation to autonomic reinnervation of the heart. The characteristic patterns of ventrolateral cardiac nerve and upon its presumed influence upon Purkinje fiber and A-V nodal automaticity and temporal dispersion of refractoriness in myocardial tissues.

Animals↗

Response of primate heart to emotional stress before and after cardiac denervation.

Eleven chair-restrained rhesus monkeys were classically conditioned to a 1-min, 900-Hz tone (CSf) followed by food and a 1-min, 3.4-5Hz tone (CSs) followed by shock. Each conditional stimulus produced large, sudden, and highly significant (P less than .01) increases in left ventricular systolic pressure (LVP), its first time derivative (d(LVP)/dt), and heart rate (HR). The animal's hearts were sugically denervated following control studies of the conditional responses. Two to four weeks later, these responses were reexamined by again presenting CSf and CSs to five surviving monkeys following a format identical to that used in the control experiments. Complete cardiac denervation virtually eliminated the sudden increases in each of the measured variables. Denervation also "unmasked" small-magnitude, delayed chronotropic and inotropic responses during CSs (but not CSf). These effects were ascribed to the action of circulating catecholamines known to be secreted during "emotional" stress. Four monkeys studied for 6 mo or more postoperatively showed evidence for varying degrees of cardiac reinnervation. Loss of nervous control of the nonhuman primate heart greatly compromises the cardiovascular response to these environmental and behavioral stress situations.

Animals↗

Autonomic neural control of cardiac rhythm: the role of autonomic imbalance in the genesis of cardiac dysrhythmia.

Cardiac dysrhythmias result from abnormalities in rate, regularity, or sequence of cardiac activation, and because of direct actions of the autonomic nervous system upon each of these properties, imbalance in this system may play an important role in the genesis of cardiac dysrhythmia. A canine model has been developed in which the extrinsic innervation of the heart is ablated with the exception of the ventrolateral cardiac nerve. This nerve is distributed primarily to the inferior atrial, AV junctional, and ventricular tissues. Following recovery from surgery, the animal is placed on a treadmill and required to perform strenuous exercise. In all of six animals which sustained repeated exercise testing over periods of 4-12 months, dysrhythmias of varying complexities were elicited. None appeared in parallel experiments conducted in control or sham-operated animals. The dysrhythmias consisted of supraventricular, AV junctional, or ventricular tachycardias with occasional premature atrial or ventricular systoles. The dysrhythmias were not influenced by atropine but were generally controlled by propranolol.

Animals↗