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Biomedical subjects

M H Laughlin

Publications and source records attributed to M H Laughlin.

At least 163 records · Page 9Linked to original sources

Pathophysiologic effects of acceleration stress in the miniature swine.

Four groups of six animals each were exposed to simulated +Gz aerial combat maneuvers (SACM). The first group was exposed to 5 SACM/d for 1 d. The other three groups were exposed to 5 SACM/d three times per week for 1 week, 1 month, and 6 months, respectively. The SACM was 100 s long and contained two 5-s +9Gz peaks. A control group of four animals was exposed to 1 d of five 100-s +1Gz exposures. All animals were unanesthetized. The animals were necropsied and the hearts were examined macro- and microscopically within 48 h of their respective acceleration regimen. Eight transmural samples were taken from each heart for hydroxyproline analysis. Subendocardial hemorrhage (scale = 0-4) and myocyte damage (damaged cells per tissue section), respectively, were greatest in the control (2.08 and 0.87) and the 1-d (2.39 and 0.84) exposure groups, declining thereafter to the lowest values in the 6-month (0.33 and 0.06) group. Hydroxyproline concentration, as an indicator of possible scar-tissue development, showed a significant positive trend with increasing time at several sample sites on the left ventricular free wall. Heart rate (HR) and ventricular ectopy were highest during the early + Gz exposures and decreased with time thereafter. Seven additional swine were chronically instrumented with an arterial catheter for blood collection during the SACM to determine hematocrit and plasma levels of catecholamines, cortisol, and protein. The animals were exposed to the same 5 SACMs/d, 3 times/week for 4 months. Plasma norepinephrine (norepi), epinephrine (epi), and cortisol increased, respectively, from mean pre-G values of 0.9 ng/ml, 0.8 ng/ml, and 10.8 micrograms/dl to mean high values of 53.8 ng/ml, 58.1 ng/ml, and 34.0 micrograms/dl during 1-d and 1-week +Gz exposure; then declined to high values of 8.6 ng/ml, 4.3 ng/ml, and 18.8 micrograms/dl after 4 months of +Gz. The decline in macro- and microscopic myocardial damage during the approximate time frame of the decline in HR, arrhythmias, norepi, epi, and cortisol suggests a causative relationship. This decline also suggests that the injury observed during +Gz exposures is the result of the emotional stress of handling, restraint, and the unfamiliar environment of the centrifuge and +Gz, to which the animal becomes accustomed with time. However, the hydroxyproline and histologic data also suggest that myocardial scar-tissue may develop as a result of multiple +Gz exposures.

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Cerebral, coronary, and renal blood flows during hemorrhagic hypotension in anesthetized miniature swine.

The purpose of these studies was to measure cerebral, coronary, and renal blood flow in miniature swine during hemorrhagic hypotension. Blood flows (BF) were measured in 16 anesthetized, female, miniature swine (35-50 kg) with the radiolabeled microsphere technique using 15-microns spheres. The animals were exposed to a standard, stepwise hemorrhagic shock protocol which set mean aortic pressure at 65, 50, 35, and 20 mm Hg for 10-15 min at each stage. Heart rate and aortic and central venous pressures were measured throughout these studies. Arterial pCO2, pO2 pH, and Hct were measured at the time of BF measurements. BFs were measured under baseline conditions and during three of the four stages of hypotension in each animal. BF was measured in the following tissues: brain (13 samples), heart (120 samples), kidney (left and right), spleen, liver, muscle, and skin. Coronary BF was consistently decreased during hypotension. Endo/Epi flow ratios were also decreased; however, they remained greater than or equal to 1.0. Renal BF and BF to most other tissues showed graded decreases with hypotension. Cerebral BF did not change significantly at any level of hypotension. The maintenance of cerebral BF in swine at such low arterial pressures (22 mm Hg) may be related to the decrease in central venous pressure (-8 mm Hg), which results in a delta P of 30 mm Hg, and/or to the swine's carotid rete mirabile.

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Muscular blood flow distribution patterns as a function of running speed in rats.

Muscle blood flow (BF) was measured using the radiolabeled microsphere technique within and among nine major muscles of rats before exercise and during treadmill walking or running at speeds of 15, 30, 45, 60, and 75 m/min. Measurements were made during exercise after 1 min of steady walking or running. Male Sprague-Dawley rats were chronically instrumented with 2 Silastic catheters, one in the ascending aorta via the right carotid artery for microsphere infusion and one in the left renal artery for arterial reference blood sample withdrawal. The preexercise results demonstrated that 1) BF to deep slow-twitch muscles was three to four times that to peripheral fast muscles (e.g., soleus and gastrocnemius BFs were 138 and 33 ml . min-1 . 100 g-1, respectively); 2) BFs to red portions within mixed muscles were three to four times those to white portions (e.g, red and white gastrocnemius BFs were 54 and 18 ml . min-1 . 100 g-1, respectively; and 3) there was a direct relationship (P less than 0.05) between BFs to muscles and their slow-twitch oxidative fiber populations. The results obtained during exercise demonstrated that 1) at the slowest speed studied (15 m/min) BFs to the red portions of muscles increased, whereas BFs to the white portions of the same muscles decreased; 2) BFs to all muscles (except soleus) were increased during running at 75 m/min when there was a range of flows of 30 ml . 100 g-1 . min-1 (white gastrocnemius) to 321 (vastus intermedius), 3) at all running speeds the increases in BF to muscles were directly related to the fast-twitch, high-oxidative fiber populations of the muscles; and 4) BFs to visceral tissues and fat were decreased during exercise.

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A method for using microspheres to measure muscle blood flow in exercising rats.

A catheter-implantation procedure allowing use of the radiolabeled microsphere (MS) technique for measuring skeletal muscle blood flow (BF) in rats during high-speed treadmill running was desired. Attempts to use existing procedures were unsuccessful. We found that Silastic catheters (0.02 in. ID X 0.037 in. OD) placed in the ascending aorta (for MS infusions) and the renal artery (for reference sample withdrawal) minimized these exercise performance problems. It was then necessary to establish that aortic MS infusions result in good MS-blood mixing. We tested the method with the following: 1) the radioactivities found in reference withdrawal samples taken from two locations in the aorta were compared after left ventricular (LV) infusion and after aortic infusion; 2) BFs to bilaterally paired tissues were compared in anesthetized and conscious rats with LV and aortic infusions; 3) the distribution of MSs in the muscles was studied histologically; and 4) BFs in bilaterally paired tissues were compared in rats with aortic MS infusions during treadmill running. The results indicate that 1) the percent difference between the radioactivities found in the proximal and distal reference withdraw samples was the same for LV and aortic MS infusions; 2) BF to bilaterally paired tissue samples was the same with both LV or aortic MS infusions; 3) the MSs were distributed uniformly within muscles, and MS aggregation was not a significant problem; and 4) BFs to bilaterally paired tissue samples were the same in exercising rats. We conclude that this technique can be used to measure muscle BF in rats running on a treadmill.

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Right ventricular pressure response to +GZ acceleration stress.

Measurements of right ventricular pressure in miniature swine were made at +Gz levels from +1 through +9 Gz. Polyethylene catheters were chronically placed in the cranial vena cava of five 2-yr-old female miniature swine (35-50 kg). The catheters were large enough to allow the introduction of a Millar pressure transducer into the venous system for placement in the right heart. The animals were fitted with an abdominal anti-G suit, restrained in a fiberglass couch, and exposed to the various +Gz levels on a centrifuge while fully conscious and unanesthetized. Right ventricular pressure and heart rate were measured during and for 2 min following 30-s exposures to each level of +Gz stress. The maximum right ventricular systolic pressure observed during +Gz was 200 Torr at +5 Gz with the maximum diastolic pressure being 88 Torr observed at +5 Gz. Mean heart rates were 200-210 beats/min at all levels of +Gz greater than or equal to +3 Gz when the animal remained stable. Mean maximum right ventricular pressures during +Gz stress were observed to increase through +5 Gz (85 Torr) and to decrease at higher levels of +Gz, indicating that through +5 Gz there is at least a partial compensation during acceleration stress. Decompensation in response to the stress began to occur during acceleration above +5 Gz with all animals decompensating during +9 Gz.

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An analysis of the risk of human cardiac damage during +Gz stress: a review.

The available information concerning the subendocardial hemorrhage, myofibrillar degeneration, and necrosis observed in miniature swine after acute +Gz exposure, is reviewed and evaluated for any possible occurrence of similar pathology in humans. It is concluded that +Gz exposure poses no significant risk for cardiac damage in humans. Three primary considerations lead to this conclusion: 1) The lesions in swine probably result from very high (toxic) levels of both sympathetic adrenergic tone to the heart and circulating plasma catecholamines acting on the cardiac cells. Most of these catecholamines appear to be released as a result of the overall stress involved in exposing conscious miniature swine to +Gz on the centrifuge, and not directly as the result of the +Gz per se. Thus, the lesions in miniature swine appear to develop as a consequence of a somewhat unique form of the porcine stress syndrome. 2) +Gz exposure is not as psychologically stressful for humans. Therefore, humans would not be expected to have, and do not appear to have, catecholamine levels (cardiac or systemic) as high as those observed in miniature swine during +Gz stress. This conclusion is supported by direct comparisons of the heart rate and plasma catecholamine levels in men and miniature swine during +Gz exposure. 3) Although a large amount of clinical cardiologic data exists from humans who have been exposed to +Gz stress, none of these data indicates any degree of cardiac damage. Even more conclusive is the absence of any cardiac damage in the heart of a human subject who had many significant +Gz exposures over a 2-year period. Thus, the pathology in miniature swine does not appear to be an acceleration phenomenon, and probably does not occur in humans exposed to +Gz stress.

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Regional distribution of cardiac output in unanesthetized baboons during +Gz stress with and without an anti-G suit.

The radiolabeled (46Sc, 85Sr, 141Ce, and 125I) microsphere (15 mu diameter) technique was used to measure blood flow to most major organs of eight chronically instrumented, unanesthetized baboons during exposure to +5 Gz and +7 Gz stress. Exposure to +5 Gz with anti-G suit support resulted in tachycardia, increased total peripheral resistance, increased aortic pressure, decreased aortic flow velocity, decreased blood flow to visceral beds, and no change in cerebral or coronary blood flows. Exposure to +7 Gz with anti-G suit support, in most animals, caused tachycardia, small increases in coronary blood flow, increased arterial pressure, decreased aortic flow velocity, and decreased blood flow to the retina, kidney, liver, spleen, pancreas, and no change in cerebral blood flow. When the animals were exposed to +Gz without anti-G suit inflation, the reductions in aortic flow velocity were more dramatic and heart-level arterial pressure was decreased below baseline values. Coronary blood flow was still increased during +Gz without anti-G suit support. Brain blood flow decreased and the regional blood flows throughout the body were decreased further than during similar +Gz exposures with a G suit. These results indicate that the baboon compensates for the +Gz-induced decrease in cardiac output by a redistribution of blood flow away from the renal and splanchnic beds in an apparent effort to maintain blood flow to the brain and heart.

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Coronary blood flow in conscious miniature swine during +GZ acceleration stress.

One of the factors determining tolerance to +GZ acceleration may be the ability to maintain adequate coronary blood flow. Consequently, the purpose of these studies was to determine the effect of acute exposure (60 s) to several levels of positive acceleration (+GZ) on total and regional coronary blood flow in conscious adult miniature swine. Blood flow was measured with the radiolabeled microsphere technique in chronically instrumented miniature swine during 60-s exposures to accelerations of +3 GZ, +5 GZ, or +7 GZ with anti-G suit support. All levels of acceleration stress caused two- to threefold increases in coronary blood flow. The regional distribution of coronary blood flow during +GZ was similar to that under resting control conditions as long as aortic diastolic pressure was maintained. All left ventricular endocardial/epicardial flow ratios were significantly greater than one, except in two animals, during exposure to +7 GZ. These were the only animals to have aortic diastolic pressures less than 100 Torr during +GZ stress. These studies indicate that, if an animal is able to compensate and maintain a cardiovascular steady State, coronary blood flow will remain adequate for myocardial needs. However, if decompensation occurs and aortic diastolic pressure falls below a critical value, subendocardial blood flow may become inadequate.

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Renal blood flow in miniature swine during +GZ stress and anti-G suit inflation.

The effects of +GZ acceleration stress on renal blood flow were studied in chronically instrumented, conscious miniature swine. Renal blood flow was determined using the radiolabeled (46Sc, 85Sr, 141Ce, and 125I) microsphere technique (29 animals) and Doppler-principle flow probes (1 animal). The results obtained with the microsphere technique indicate that +GZ exposure with anti-G suit support caused decreases in renal blood flow throughout the kidney, and that renal blood flow remains decreased for 1-10 min after +GZ stress. Medullary blood flow appeared to recover after +GZ exposure more rapidly than cortical blood flow. The flow probe data also indicate that +GZ stress with or without anti-G suit support results in decreases in renal blood flow, and that anti-G suit inflation in the absence of +GZ can also cause significant decreases. We conclude that the reductions in renal blood flow observed in miniature swine, during +GZ stress with anti-G suit support, may be due to a combination of direct anti-G suit interference and +GZ-induced reflex increases in alpha-constrictor sympathetic tone to the renal vascular bed.

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Alterations in cardiac rate and rhythm in miniature swine during simulated aerial combat maneuver +Gz stress.

Electrocardiograms (McFee-axial reference system) were recorded from 18 chronically instrumented, conscious, female miniature swine before, during, and after exposures to +Gz stress. The animals were exposed to five simulated aerial combat maneuver (SACM) type acceleration profiles which spanned approximately 106 s and included two 5-s +9Gz peaks. A 5-min rest period separated each SACM exposure. Maximum heart rates during +Gz decreased over the course of the 5 SACM's-241 +/- 4 b/m and 224 +/- 5 b/m for the first and last exposures, respectively. Resting heart rates obtained 5 min after each SACM exposure were steadily increased from a control of 86 +/- 5 b/m to a final of 129 +/- 8b/m. Of the 18 animals studied, 10 developed arrhythmias during +Gz, or within the first minute after +Gz exposure. Arrhythmias exhibited included premature atrial and ventricular contractions, intraventricular conduction defects, sinus arrhythmias, premature junctional contractions, atrial bigeminy, ectopic atrial and ventricular rhythms, complete A-V dissociation, left anterior arborization-block, and junctional rhythms with aberrant conduction. While arrhythmias were not uncommonly observed during +Gz, most occurred at the end of the SACM profile or immediately following the SACM.

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The importance of myocardial perfusion in the pathogenesis of the cardiac pathology associated with +Gz exposure in miniature swine.

Minor cardiomyopathy has been associated with exposure of miniature swine to levels of high sustained +Gz which can be attained routinely in new USAF high-performance aircraft. One possible cause of these lesions is total or regional myocardial ischemia. To test this hypothesis, regional coronary blood flow was measured with the radiolabeled microsphere technique in chronically instrumented miniature swine during 60-s exposures to +3Gz, +5Gz, or +7Gz. Acceleration exposure resulted in detectable left ventricular subendocardial hemorrhage in 1 of 5 animals exposed to +3Gz, in 7 of 8 animals exposed to +5Gz and in all 8 animals exposed to +7Gz. All levels of +Gz stress caused 2-3 fold increases in coronary blood flow. The regional distribution of coronary blood flow during +Gz was similar to that under resting control conditions as long as aortic diastolic pressure was maintained. There was no clear evidence of total or regional myocardial ischemia during +Gz or of any relationship between regional coronary blood flow and the presence of subendocardial hemorrhage. It is concluded that myocardial ischemia is not a primary factor in the pathogenesis of the cardiac lesions associated with the exposure of miniature swine to +Gz stress.

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Frank orthogonal vectorcardiograms in humans during and after exposure to +Gz acceleration stress.

Frank orthogonal vectorcardiograms (VCGs) were recorded from 10 subjects prior to, during, and for 15 min after exposures to +3Gz , +5Gz, and +7Gz. The order of acceleration exposure was randomized, with the individual exposures separated by at least 1 week. Standard USAF anti-G suits were worn by all subjects. Detailed analysis of the scalar lead electrocardiograms revealed no abnormalities. There were no consistent signs of conduction disturbances or ischemic ST-T segment changes. The QRS axis of the VCG demonstrated posterior rotation in the sagittal plane and counterclockwise rotation in the transverse plane during +Gz stress. The changes in the VCGs recorded during +Gz stress appeared to be related to rotational changes of the heart due to mechanical stress and/or motion within the thorax. There were no ECG or VCG changes indicative of myocardial ischemia and/or damage during or after +Gz stress.

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Coincident loss of consciousness and ventricular tachycardia during +GZ stress.

The environment of the advanced fighter aircraft represents a unique combination of stressful factors. Each of the individual stresses is hazardous, with the summation of these factors possibly resulting in an additional risk for sudden in-flight incapacitation. Advanced fighter aircraft are capabble of producing both rapid onset and high sustained +GZ forces which, on occasion, can exceed the tolerance limits of the pilot. The +GZ forces encountered during aerial combat maneuvering are physiologically stressful and have a profound effect on the regulatory mechanisms of the body. The influence of these stresses, including +GZ stress, on the autonomic nervous system is complex. The overall normal regulation of the cardiovascular system depends on a balance between both branches of the autonomic nervous system. An imbalance between sympathetic and parasympathetic tone can result in cardiac dysrhythmias and symptoms not conducive to safe and effective flight. An episode of ventricular tachycardia, coincident with an episode of loss of consciousness, was observed in an apparently healthy aircrewman during +GZ stress on the USAF School of Aerospace Medicine human centrifuge. The implications of autonomic imbalance in the production of similar potentially hazardous dysrhythmias and symptoms in the multistress environment deserve more in-depth investigation.

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Coronary blood flow during +Gz stress in +Gz conditioned adult miniature swine.

Four female adult miniature swine were acceleration conditioned for a period of 1 month using repeated acute exposure to simulated aerial combat maneuver profiles which exposed the animals to an average of +4.5G, for 106s. This period of conditioning produced adaptation as evidenced by decreased maximal heart rates during +Gz and by the absence of any +Gz induced gross cardiac pathology. Coronary blood flow was measured in these conditioned animals with the radiolabeled microsphere technique. Blood flows were measured under resting conditions, during 60s exposures to +3Gz and +5Gz and 10 min after +5Gz exposure. Coronary flow was increased 2-3 fold during +3Gz and +5Gz. The regional distribution of coronary blood flow during +Gz was similar to that under resting control conditions. There were no significant differences between coronary blood flows during +Gz in these conditioned animals and the values previously reported from the initial exposure of miniature swine to similar levels of +Gz. These results indicate that 1 month of acceleration conditioning of the types used in these studies has no significant effect on the response of coronary blood flow to +3Gz and +5Gz stress.

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Use of microspheres in measurement of regional blood flows during +GZ stress.

The use of the radiolabeled microsphere technique for the study of the effects of +GZ acceleration on regional blood flow is examined. A theoretical analysis of the limits of this technique in a high acceleration environment is presented. Chronically implanted, electromagnetic, aortic flow probes were used to determine the relationship between aortic blood flow velocity and +GZ acceleration in conscious adult miniature swine. It was found that conscious straining adult miniature swine, with the assistance of an inflated anti-G suit, are able to compensate quite well to acceleration levels less than or equal to +7 GZ. Exposure to +9 GZ often resulted in unstable cardiovascular states involving relative bradycardia, often progressing to asystole, declining aortic blood pressure, and markedly diminished cardiac outputs approaching zero. It was found that, if aortic pressure and heart rate attain a relatively steady state during acceleration, and if heart level mean aortic pressure is greater than or equal to 100 Torr, the application of the microsphere technique during +GZ acceleration is theoretically valid. This hypothesis was tested using the microsphere technique (9.0 +/- 0.8 microns diam) in conscious miniature swine during exposure to +GZ acceleration. It is concluded that within the defined limits the radiolabeled microsphere technique is as accurate for use during acceleration studies as it is for use in routine laboratory studies.

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Concurrent loss of consciousness and sino-atrial block during +Gz stress.

Current USAF fighter aircraft easily exceed human physiologic limits with their rapid onset of head-to-foot acceleration forces (+Gz). Sudden in-flight incapacitation caused by these increased +Gz forces could be disastrous with loss of materiel and human life. The physiologic mechanisms responsible for loss of consciousness (LOC) secondary to high +Gz must be fully understood so that maximum protection against it can be provided. An interesting case of an episode of LOC with concurrent sino-atrial block occurring during a relaxed rapid onset (1 G/s) centrifuge run is presented. The patient was undergoing flight medical evaluation for an episode of syncope, etiology unknown. An unusual characteristic of the patient was his high level of endurance training. The possibility of an excessive increase in vagal tone, developed by endurance training, is discussed as a probable etiology for this patient's prolonged time of incapacitation evidenced after +Gz-induced loss of consciousness.

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Regional cerebral blood flow in conscious miniature swine during high sustained +Gz acceleration stress.

The two major factors limiting performance during high +Gz acceleration stress are loss of vision, and loss of consciousness. These symptoms are believed to occur as a result of insufficient blood flow to the retina and brain. This study was conducted to determine the effects of +Gz stress on regional cerebral blood flow. Cerebral blood flow (CBF) was measured in 22 conscious, female, miniature swine with the radio-labeled microsphere technique. Acceleration exposures consisted of 60-S plateaus at +3Gz, +5Gz or +7Gz. Microsphere infusions were made before, during, 1.0-6.0 min after, and 10 min after +Gz. Blood flow to the retina was significantly decreased during exposure to +5Gz and ceased during exposure to +7Gz stress. Mean, resting control CBF was 34 +/- 4 ml/min/100 g. Exposure to +3Gz and +5Gz had no significant effect on CBF. Exposure to +7Gz appeared to cause a redistribution of CBF, with blood flow to the brain stem being preserved and flow to the cerebrum being diminished.

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