Acute Aortic Stenosis Research Articles

Nexus Between Human Thermoregulation and Cardiovascular Functions—A Preliminary Simulation for a Moderate Variation of Temperature

AbstractThough the interaction between cardiovascular functions and thermoregulation is enormously complex yet immensely important, very little effort to date has been spent to simulate it from a system point of view. The present work aims at simulating the mutual interaction of human thermoregulation and cardiovascular functions by combining simple models of these two systems. While for thermoregulation, a lumped parameter multi-node model has been developed, a SIMULINK-based approach of electrical analogy has been taken for the cardiovascular system. These two models are coupled by different physiological and control actions, represented by well-established correlations. Three case studies have been conducted. In the first case, thermoregulation of a healthy human being is considered for a prescribed temperature cycle of moderate variation. Under heat stress, cardiac output increases by a joint effect of heart rate and stroke volume while under the cold condition, the variation of the cardiac output is less and is primarily governed by the heart rate. For the case of a reduced ejection fraction of the left ventricle, though there is a notable decrease in skin blood flow, negligible variation in skin and core temperature is observed. In the case of acute aortic stenosis, it is found that the blood pressure falls severely from its normal level causing hypotension and is further aggravated even under moderate heat stress. Such a situation might have further consequences like heat stroke. Finally, the limitations of the present study have been highlighted and suggestions have been made for further improvement.

Nonbacterial Thrombotic Endocarditis Leading to Acute Heart Failure due to Aortic Stenosis in a Patient with Lung Cancer

We herein report an autopsied case of a patient with adenocarcinoma of the lungs who developed nonbacterial thrombotic endocarditis (NBTE) that caused acute heart failure (AHF) due to acute aortic stenosis (AS). A 37-year-old man was admitted to our hospital due to chest pain and fever. He was diagnosed as having Stage IV lung cancer. Following the administration of chemotherapy, the patient presented with acute onset of dyspnea. He was diagnosed with having AHF based on his clinical course and physical findings, and ultimately he died without responding to treatment. The autopsy revealed that NBTE caused acute AS leading to AHF.

Translational mechanisms accelerate the rate of protein synthesis during canine pressure-overload hypertrophy.

This study examined how translational mechanisms regulate the rate of cardiac protein synthesis during canine pressure overload in vivo. Acute aortic stenosis (AS) was produced by inflating a balloon catheter in the ascending aorta for 6 h; sustained AS was created by controlled banding of the ascending aorta. AS caused significant hypertrophy as reflected by increased left ventricular (LV) mass after 5 and 10 days. To monitor LV protein synthesis in vivo, myosin heavy chain (MHC) synthesis was measured by continuous infusion of radiolabeled leucine. Acute AS accelerated the rate of myosin synthesis without a corresponding increase in ribosomal RNA, indicating an increase in translational efficiency. Total MHC synthesis (mg MHC/LV per day) was significantly increased at 5 and 10 days of sustained AS. Total MHC degradation was not significantly altered at 5 days of AS but increased at 10 days of AS in concordance with a new steady state with respect to growth. Translational capacity (mg total RNA/LV) was significantly increased after 5 and 10 days of AS and was preceded by an increase in the rate of ribosome formation. MHC mRNA levels remained unchanged during AS. These findings demonstrate that cardiac protein synthesis is accelerated in response to pressure overload by an initial increase in translational efficiency, followed by an adaptive increase in translational capacity during sustained hypertrophic growth.

Limited left ventricular inotropic response to exercise in early phase of pressure overload in dogs.

To study the mechanisms of myocardial adaptation to increased stress in the early phase of left ventricular (LV) pressure overload, 12 dogs were instrumented with LV micromanometer, LV dimensional ultrasonic crystals, aortic catheter, and aortic occluder cuff. After recovery, animals performed graded exercise with acute aortic stenosis (AS) or sustained (24 h) aortic stenosis (SS). At baseline, LV functional parameters with SS were not different from those obtained with AS. LV peak pressure increased similarly during exercise with AS or SS, but LV peak dP/dt was lower with SS than with AS (peak values, 6,292 +/- 525 vs. 7,570 +/- 432 mmHg/s; P < 0.05). LV end-diastolic pressure increased from 9.7 +/- 1.7 to 21.4 +/- 3.3 mmHg (P < 0.05) during exercise with SS, but was unchanged with AS. The decrease of the time constant of isovolumic pressure fall during exercise was significantly smaller after SS than during AS (P < 0.05). In addition, the percentage of subendocardial wall thickening did not increase during exercise with SS (30.3 +/- 3.6%), while it increased significantly with AS (from 29.3 +/- 3.3 to 39.4 +/- 4.5%; P < 0.01). Plasma catecholamine levels were similar at baseline and increased to similar levels during exercise with AS and SS. In the early phase of pressure overload, we conclude that exercise capacity is maintained but that the LV inotropic response to exercise is modified with an altered relaxation process and a lesser utilization of subendocardial inotropic reserve.

Raised plasma concentrations of endothelin-1 and -3 in marmosets with acute aortic stenosis: no relation to the renin-angiotensin system.

Plasma levels of endothelin (ET), plasma renin activity (PRA) and angiotensin II (Ang II) were measured in anaesthetized marmosets exposed to acute aortic stenosis proximal to the renal arteries. In vehicle experiments, ET rose from 5 +/- 2 to 38 +/- 4 pg ml-1, PRA from 5 +/- 2 to 99 +/- 21 ng ml-1 h-1 and Ang II from 21 +/- 4 to 213 +/- 76 pg ml-1. Administration of renin inhibitor and angiotensin converting enzyme inhibitor reduced PRA and Ang II to control levels, while the plasma levels of ET increased further (51 +/- 10 and 71 +/- 16 pg ml-1, respectively). During aortic stenosis the two isoforms ET-1 and ET-3 appeared in the circulation, while in conscious control animals only ET-1 was found. It is concluded that the increased plasma levels of ET in our primate model could not be ascribed to the increased circulating levels of PRA and Ang II.

Intracoronary veratrine and acute aortic stenosis modify renal responses to hypotension in conscious dogs

The present study was undertaken to determine whether intracoronary (left circumflex) veratrine (ICV) infusions and increases in left ventricular (LV) systolic pressure influence renal circulatory and excretory function in chronically instrumented conscious dogs (n = 19). Thirty minutes of ICV infusions decreased arterial pressure by 15-20 mmHg, but heart rate, urine flow, sodium excretion, and free water clearance did not change. Intravenous nitroprusside infusions, which also lowered arterial pressure by 15-20 mmHg, increased heart rate while urine flow, sodium excretion, and free water clearance were significantly decreased. Heart rate and renal excretory function also did not change during a 15- to 20-mmHg decrease in arterial pressure when LV systolic pressure was simultaneously raised to approximately 170 mmHg by ascending aortic occlusion. The topical application of a local anesthetic in the region of the left main coronary artery abolished the Bezold-Jarisch reflex and the attenuation of hypotension-induced salt and water retention and tachycardia by ICV. Renal plasma flow and glomerular filtration rate were not altered during any of the above experimental treatments. These results suggest that in the conscious dog chemical and mechanical stimulation of LV sensory receptors with afferents in the pericoronary region can modulate the neurohumoral reflex control of renal excretory function independent of local filtration effects.

Modification of force-interval relations during early adaptation to pressure overload in dogs

Ventricular function was analyzed in the end-systolic and end-ejection pressure-volume diagrams in seven conscious dogs during acute aortic stenosis (AS) and sustained stenosis (SS) 24 h later. Dogs were previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring left ventricular major and minor axes and parietal wall thickness. The end-ejection pressure-calculated volume points were significantly shifted to the left during SS as compared with those obtained during AS both during a regular atrial pacing (150 beats/min) and during spontaneous heart rate. Postpacing beats were not different during AS and SS. During AS, end-systolic volume was larger after short intervals (SI) between beats (22.5 +/- 1.6 ml) than after long intervals (LI; 20.8 +/- 1.7 ml) for a smaller end-systolic pressure (P less than 0.001). This difference was minimal during SS. When SS was compared with AS, the end-systolic and end-ejection pressure-volume points were significantly shifted to the left after SI but not after LI. This suggests an acceleration of the restitution process during SS that modifies ventricular force-frequency relations and increases ventricular function as compared with AS, particularly for high heart rates.

Effect of Aortic Stenosis on Oxygen Balance in Partially Ischemic Myocardium

Valvar aortic stenosis can result in myocardial underperfusion with or without coronary obstruction. The purpose of this study was to determine how hearts with valvar aortic stenosis without hypertrophy can maintain their oxygen supply/consumption balance with partial left anterior descending coronary artery (LAD) occlusion. Open-chested, anesthetized dogs ( n = 9) were subjected to mild valvar aortic stenosis and then to a reduction of LAD flow to 50% of baseline, while controls ( n = 9) received partial LAD occlusion without aortic stenosis. Blood flows were determined before and after aortic stenosis and after LAD occlusion using radioactive microspheres. The hearts were then removed for microspectrophotometric analysis of regional venous and arterial oxygen saturation. Aortic stenosis resulted in a pressure gradient of approximately 50 mm Hg, representing mild aortic stenosis. Only a slight increase in myocardial blood flow was seen with aortic stenosis. Ischemia resulted in a significant drop in blood flow in control (40%) and aortic stenosis (55%) animals compared with their own preocclusion values. These ischemic region flows were not different from each other. Aortic stenosis itself did not alter oxygen extraction, although partial occlusion similarly increased extraction for all groups in the ischemic zone. The LAD occlusion resulted in a decreased oxygen consumption in the occluded region of all groups, with no differences noted between control and aortic stenosed animals. Thus, mild, acute aortic stenosis without hypertrophy does not appear to significantly increase the severity of an ischemic episode precipitated by partial LAD occlusion.

Acute aortic stenosis in the conscious dog: effects of inotropic state on heart rate.

Effects of acute distension of the left ventricle on heart rate were studied in conscious, instrumented dogs. In intact dogs, increasing left ventricular (LV) systolic pressure by a maximum of 77.6 +/- 3.6 mmHg from a control of 123.1 +/- 3.6 and LV end-diastolic pressure by a maximum of 24.1 +/- 2.0 mmHg from a control of 8.5 +/- 1.3 did not result in any consistent change in heart rate. Reduction of arterial pressure with sodium nitroprusside caused an increase in heart rate to 143.9 +/- 13.8 beats/min. With baroreceptors unloaded, increasing LV pressure by a similar degree as in the control group now resulted in consistent and significant bradycardia. Removal of arterial baroreceptors in a final group of dogs abolished the baroreflex. Increasing LV pressure by aortic stenosis now resulted in a stimulus-dependent decrease in heart rate that was significantly greater than that in the nitroprusside group. Both administration of atropine and bilateral cervical vagotomy abolished bradycardia. The second part of this study was concerned with effects of increases in LV inotropic state on heart rate change evoked by aortic stenosis. Each group was infused with intracoronary epinephrine. Infusion of epinephrine (12.5-50.0 ng . kg-1 . min-1) significantly increased LV dP/dt without any significant change in heart rate or mean arterial blood pressure. Aortic stenosis during epinephrine infusion did not result in any significant difference in heart rate responses in any group studied. It is concluded that LV distension can cause a reduction in heart rate that is opposed by the presence of arterial baroreceptors and that increases in LV myocardial contractility do not have any effect on the magnitude of this response.

Left ventricular adaptation to sustained pressure overload in the conscious dog.

The early adaptation to aortic stenosis was studied in eight conscious dogs previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring left ventricular minor equator, left ventricular major axis, and ventricular wall thickness. Data were compared during control, acute inflation of a supravalvular aortic cuff occluder and 24 hours after aortic stenosis with and without beta-blockade. Acute aortic stenosis increased peak systolic pressure and end-systolic pressure with a decrease of percent systolic shortening of minor diameter (% delta L). Twenty-four hours after aortic constriction for heart rates, end-diastolic dimensions, and systolic pressures similar to those measured during acute aortic stenosis, % delta L was significantly increased, compared with acute aortic constriction, and was close to control values. End-systolic diameter was not significantly different from control during sustained pressure overload, although end-systolic stress was increased by 26.7 +/- 6.1% (P less than 0.01 with control), representing a leftward shift of the end-systolic stress-diameter relation. Similar results were obtained under beta-blockade. We conclude that there is, in this model of moderate pressure overload, a nonsympathetic increased inotropic state very early after aortic constriction.

Ultrastructural basis of acute left ventricular failure from severe acute aortic stenosis in the rabbit

The haemodynamic and morphological data of experimental left ventricular failure due to acute aortic constriction in the rabbit have been studied. A progressive decrease of contractility is preceded by an initial transitory increase in contractility. The sarcomere length/filling pressure curve demonstrates that after constriction of the aorta a decrease in passive extensibility of sarcomeres occurs despite the fact that the ventricular volume is significantly increased in animals with aortic stenosis. Variation in passive lengthening of myofibres, myofibrillar degeneration including fragmentation of Z lines and mitochondrial alterations are the most important morphological changes observed.

Role of lysosomal enzymes in adaptation to simulated high altitude by myocardium subject to the effects of acute aortic stenosis or isoproterenol

Training of rats to the effect of interrupted high altitude results in the increase in total activity of lysosomal enzymes of acid DNase, RNase and phosphatase of the myocardium. The activity of the “bound” fraction of the enzymes is increased most. The resistance of lysosomal systems of the heart in adapted animals to the effects of acute hyperfunction and of isoproterenol administration is increased; the activity of the three lysosomal enzymes decreases to a much lesser extent than in the non-adapted animals.