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Biomedical subjects

R S Reneman

Publications and source records attributed to R S Reneman.

At least 199 records · Page 11Linked to original sources

Effect of blood gases and pH on thromboembolic reactions in rabbit mesenteric microvessels.

The influence of changes in systemic blood gas and pH values on the thromboembolic reaction following wall puncture was studied in rabbit mesenteric arterioles and venules (diameter 20-40 microns), using intravital video-microscopy. Under normal circumstances the number of emboli produced was higher in arterioles than in venules (6 and 1, respectively). The initial thrombus growth, the number of emboli produced per vessel and the total duration of the embolisation period were not significantly influenced by changes in blood gas and pH values in both arterioles and venules. Therefore, the observed difference in thromboembolic reaction between arterioles and venules cannot be explained by differences in blood gas and pH values in these microvessels. Since reduced velocity, as a measure of wall shear rate, did not correlate with the thromboembolic reaction in arterioles or venules, fluid dynamics can also not explain the difference, indicating that the thrombogenic or antithrombogenic activity of arteriolar and venular walls differs following injury. A combination of hypercapnia and hypoxia was found to result in a prolongation of the average time period needed to produce a new embolus in both vessel types. This prolongation in embolus production time was largely due to the occurrence of periods, in which the thrombus did not grow, reflecting hampering of the adhesion and aggregation of blood platelets to a growing thrombus under hypercapnic/hypoxic conditions.

Animals↗

Effect of ketanserin on macrocirculatory and microcirculatory blood flow in patients with intermittent claudication. A prospective randomized study.

The effect of ketanserin on macrocirculatory and microcirculatory blood flow was investigated in a placebo-controlled, double-blind trial in 11 patients suffering from intermittent claudication using Doppler velocimetry and intravital skin capillary microscopy, respectively. After 1 year of treatment no significant change was observed either in the ketanserin or the placebo group. It appears that ketanserin has no significant effect on macrocirculatory blood flow and microcirculatory nutritional skin blood flow in patients with intermittent claudication.

Aged↗

Dynamics of left ventricular wall and mitral valve mechanics--a model study.

The relation between global left ventricular pumping characteristics and local cardiac muscle fiber mechanics is represented by a mathematical model of left ventricular mechanics in which the mitral valve papillary muscle system is incorporated. The wall of the left ventricle is simulated by a thick-walled cylinder. Transmural differences in fiber orientation are incorporated by changing the direction of material anisotropy across the wall. The cylinder is free to twist. The upper end of the cylinder is covered by a thin, flexible sheet, representing the base of the left ventricle. The mitral valve is incorporated in this sheet. The tips of the mitral leaflets are connected by chordae tendineae to the papillary muscles which are attached to the bottom of the cylinder. Canine cardiac cycles were simulated for various end-diastolic values of left ventricular volume (25-120 ml, control 60 ml), left atrial pressure (0-2.7 kPa, control 0.22 kPa) and aortic pressure (5-11 kPa, control 11 kPa). In this wide range of preload and afterload mechanical loading of the muscle fibers appeared to be distributed quite evenly (SD: +/- 5% of control value) over all muscular structures of the left ventricle, including the papillary muscles.

Animals↗

Myocardial blood flow and oxygen consumption after aortic cross-clamping.

The effect of four repetitive periods of 10 min global ischemia, followed by 15 min of reperfusion on myocardial blood flow and oxygen consumption at 34 degrees C (group N) and 25 degrees C (group H) were studied in comparison with that of 60 min continuous ischemia combined with multidose St. Thomas Cardioplegia (group C) in dogs on cardiopulmonary bypass (CPB). Two groups, in which a protocol comparable to the groups N and H, respectively, but without repetitive periods of ischemia was followed, served as control. In all groups a hyperemic response was observed after release of aortic cross-clamping (AC). Myocardial blood flow was not diminished at the end of CPB as compared to the values at the start of CPB. We conclude that the no-reflow phenomenon did not occur after these procedures of intermittent or continuous AC. Immediately following release of AC the arterial-coronary sinus difference of oxygen content reached a peak value in groups N and H indicating rapid replenishment of the low tissue oxygen content. These peak values appeared to be much smaller after cardioplegia. After 10 min of reperfusion a significant lower oxygen consumption was observed at 25 degrees C (0.2 mumole.g-1.min-1 O2) as compared to 34 degrees C (1.5 mumole.g-1.min-1 O2). This difference cannot be explained by temperature alone because oxygen consumption did not decrease below 0.5 mumole.g-1.min-1 in the control group of dogs put on CPB at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An improved method to correct the QT interval of the electrocardiogram for changes in heart rate.

The adequacy of the Bazett formula to correct for heart rate-induced changes in the QT interval of the electrocardiogram has been frequently questioned. In the present study, a simple linear equation was derived, which in anesthetized dogs corrects more adequately for changes in heart rate than the Bazett formula. Regression analysis of experimental data yielded the following equation: QTc = QT - 0.087 (RR - 1000) = QT - 87 (60/HR - 1). The reliability of this equation was investigated in experiments on anesthetized dogs with different cardioactive drugs with a known mechanism of action.

Amiodarone↗

Metabolic and haemodynamic changes in the heart during the early phase of cardiopulmonary bypass: I. Clinical observations.

Knowledge of the effects of cardiopulmonary bypass on the myocardium and on cardiac function is limited. We therefore studied changes in haemodynamics and myocardial metabolism during the initial phase of cardiopulmonary bypass in two patient groups. In one group "normothermia" (34 degrees C) was used while on bypass, with an empty beating heart; in the other group hypothermia (range 27-33 degrees C) with ventricular fibrillation was used. Mean aortic pressure and myocardial oxygen consumption decreased significantly in both groups after instalment of CPB. The arterial-coronary sinus differences in lactate changed to negative values within 5 min of the start of bypass, indicating release instead of uptake of lactate. This release was maintained during the observation period and increased significantly in the hypothermic patient group when the ventricles were fibrillating. Therefore in patients undergoing aorto-coronary bypass surgery, detrimental changes in the myocardium must be anticipated during the initial phase of cardiopulmonary bypass prior to aortic cross clamping.

Aorta↗

Metabolic and haemodynamic changes in the heart during the early phase of cardiopulmonary bypass: II. Animal experiments.

A significant release of lactate instead of uptake was observed during the first 10 min of cardiopulmonary bypass preceding aorto-coronary bypass surgery in human patients. To clarify these findings in more detail, myocardial lactate and oxygen metabolism was studied in healthy dog hearts subjected to a protocol similar to the clinical situation. In one group (n = 11) normothermia at 34 degrees C was used with an empty beating heart, and in the other group (n = 11) hypothermia with ventricular fibrillation was applied. Within the first 10 min of bypass no significant changes in high energy phosphates were observed in myocardial biopsies. However, a marked decrease in mean aortic blood pressure and a simultaneous lowering in oxygen consumption was observed in both groups after instalment of bypass. An initial shift from lactate uptake to lactate release occurred while on bypass in the normothermia group. After 10 min of bypass, lactate uptake was restored in hearts of both groups. Therefore, the lactate release during the initial phase of bypass in patients originates both from the instalment of the bypass and from (local) inadequate perfusion, which is most likely to be due to stenosed coronary arteries.

Animals↗

Ketanserin in the treatment of pulmonary hypertension after valvular surgery: a comparison with sodium nitroprusside.

In a prospective randomized trial in patients with a history of preoperative pulmonary hypertension who were undergoing surgery for valvular replacement or annuloplasty, the effects of ketanserin (KET) (12 patients) and sodium nitroprusside (SNP) (14 patients) on the systemic and pulmonary circulation and pulmonary shunt fraction (Qsp/Qt) were studied in the immediate postoperative period. The agents were administered at the moment that pulmonary arterial pressure (PAP) tended to rise and cardiac output started to decrease. After administration, systemic arterial BP, PAP, systemic and pulmonary (PVR) vascular resistance, and right ventricular stroke work (RVSW) decreased significantly in both groups. The decrease in mean pulmonary arterial pressure (p less than .01), PVR (p less than .01), and RVSW (p less than .05) was significantly more pronounced in the KET than in the SNP group. Qsp/Qt significantly (p less than .001) increased in the SNP group, but significantly (p less than .05) decreased in the KET group; the response was significantly different between the two groups (p less than .001). In six patients, SNP converted pacemaker-dependent heart rate into a spontaneous rhythm, whereas this occurred in only one patient in the KET group. We concluded that KET, as opposed to SNP, reduces PVR without increasing Qsp/Qt in the lung, which is particularly advantageous in patients after valvular surgery.

Drug Evaluation↗

Verapamil and nebivolol improve carotid artery distensibility in hypertensive patients.

The effects of verapamil (a calcium antagonist) and nebivolol (a novel, selective beta 1-adrenoceptor blocker) on carotid artery distensibility and cross-sectional compliance were studied non-invasively in hypertensive patients with the use of a high-resolution multigate pulsed Doppler system. Arm blood pressure measurements were made with an automated device (Dinamap). After a 4-week washout period, 19 patients (aged 21-73 years) with essential hypertension entered a double-blind randomized placebo-controlled crossover study with 120 mg verapamil or placebo three times a day for 4 weeks. After the administration of verapamil, carotid artery distensibility and cross-sectional compliance were significantly larger (P less than 0.05) than after placebo. Using the same protocol, 29 patients (aged 25-70 years) were given 5 mg nebivolol or placebo once a day for 4 weeks. After the administration of nebivolol, carotid artery distensibility and cross-sectional compliance were significantly larger (P less than 0.05) than after placebo. In both studies no significant differences in diameter and pulse pressure were found between placebo and verapamil or nebivolol. Blood pressure was decreased similarly with both verapamil and nebivolol. These results indicate that both verapamil and nebivolol favourably influence carotid artery distensibility and cross-sectional compliance of the common carotid artery, resulting in a better management of the systolic pressure pulse. The improved carotid artery distensibility may help to protect the patient against atherosclerotic complications of hypertension.

Adrenergic beta-Antagonists↗

Assessment of the orifice diameter by a multigated pulsed Doppler system in children with congenital semilunar valve stenosis.

This study investigated whether the jet diameter measured by a multigated pulsed Doppler system could be used to assess the severity of valve disease in children with pulmonary (n = 11) or aortic (n = 4) valve stenosis. The results obtained were compared with those obtained at cineangiography and at operation. Multigated pulsed Doppler examination of a stenosed valve showed a region of relatively high velocities in the velocity profile (jet flow). There was good agreement between the diameter of the disturbed region on the Doppler echocardiogram and the diameter of the jet on the lateral angiocardiogram. In severe valve stenosis the agreement between the valve diameters measured by multigated pulsed Doppler and at operation was also good. In less severe valve stenosis Doppler measurements systematically underestimated the valve diameter at operation. It is likely that the functional opening of a semilunar valve is a more relevant estimate of the degree of stenosis than the anatomical measurement of the orifice. The findings of this study indicate that multigated pulsed Doppler systems are useful in the noninvasive diagnosis of stenotic valve disease.

Aortic Valve↗

Degradation of adenine nucleotides in ischemic and reperfused rat heart.

Complete cessation of flow in isolated rat hearts for 90 min resulted in a gradual breakdown of ATP and concomitant accumulation of degradation products, such as adenosine, inosine (major break-down product), hypoxanthine, and, to a lesser extent, xanthine. After 45 min of ischemia, the content and relative composition of purines hardly changed, whereas the AMP content continued to rise. This finding points to constraints on AMP degradation and flux through the degradation pathway from adenosine to uric acid in the ischemic heart. In myocardial preparations, the cells of which were deliberately disrupted by freezing and thawing before anoxic incubation, AMP did not accumulate and was finally converted to hypoxanthine. These results indicate that compartmentalization of substrates and enzymes is responsible for the observed preferential accumulation of AMP and inosine in the ischemic heart. Inhibition of hypoxanthine degradation is explained by the absence of oxygen. Restoration of flow and oxygen supply abolished the inhibition of metabolic flux. Accumulated purines were released into the coronary effluent and, concomitantly, further metabolized. Comparison of tissue levels of hypoxanthine, xanthine, and uric acid before reperfusion and the amounts released during reperfusion indicates that in rat myocardium substantial amounts of potentially hazardous xanthine oxidase-derived reactive oxygen species are likely to be formed during the early reperfusion phase.

Adenine Nucleotides↗

Exercise-induced focal skeletal muscle fiber degeneration and capillary morphology.

The relationship between exercise-induced focal muscle fiber degeneration and changes in capillary morphology was investigated in male Wistar rats. Untrained animals ran on a treadmill for 1 h at submaximal intensity and were killed 0, 6, or 24 h after running. Nonexercised rats served as controls. In situ perfused soleus muscles were prepared for electron microscopy. Micrographed cross sections were quantitatively analyzed for parameters indicative of capillary blood flow or transcapillary exchange. Capillary lumina were ovally rather than circularly shaped, and no indications for obstruction of blood flow at the capillary level were found. Endothelial cells and their organelles had a normal appearance in all groups. However, immediately after exercise, capillaries showed a decreased thickness of their endothelium and basal membrane, probably caused by dehydration. Six hours after exercise, muscle fibers were swollen (28% increase in cross-sectional area), resulting in a slightly increased diffusion distance. This fiber swelling was not associated with an increase in muscle water content, a finding for which no explanation could be found. Twenty-four hours after the animals ran, capillaries located near degenerated muscle fibers had an increased cross-sectional luminal area and an increased luminal circumference. This effect decreased gradually with increasing distance from the degenerated fiber area. The present morphometric results do not support the hypothesis that changes in capillary morphology primarily contribute to exercise-induced focal muscle fiber degeneration.

Animals↗

Lipid alterations in isolated, working rat hearts during ischemia and reperfusion: its relation to myocardial damage.

Disturbances in lipid metabolism may play an important role in the onset of irreversible myocardial damage. To investigate the effect of ischemia and reperfusion on lipid homeostasis and to delineate its possible consequences for myocardial damage, Krebs-Henseleit-perfused, working rat hearts were subjected to various periods of no-flow ischemia (10 to 90 minutes) with or without 30 minutes of reperfusion. During ischemia, the rise in nonesterified fatty acids (NEFAs) was preceded by the accumulation of substantial amounts of glycerol, indicating the presence of an active triacylglycerol-NEFA cycle. The subsequent rise in NEFAs (from 0.25 to 1.64 mumol/g dry residue wt after 90 minutes [means]) coincided with the reduction of ATP to values lower than 10 mumol/g dry wt and the rise of AMP, a potent inhibitor of acyl-coenzyme A synthetase, to values exceeding 2 mumol/g dry wt, making the latter compound a good candidate to hamper the turnover of endogenous lipids during prolonged ischemia. Reperfusion resulted in an additional rise in NEFAs (up to 4.1 mumol/g dry residue wt after 60 minutes of ischemia). Neither ischemia nor reperfusion resulted in significant decreases in the tissue content of triacylglycerols and the various phospholipids. During reperfusion recovery of stroke volume was still adequate at tissue NEFA levels thought to be incompatible with normal mitochondrial function. A positive correlation (r = 0.81) was found between NEFA content of reperfused hearts and cumulative release of lactate dehydrogenase during reperfusion. Accordingly it is concluded that 1) reperfusion results in additional changes in myocardial lipid homeostasis, 2) the accumulating NEFAs are compartmentalized, possibly at the cellular level, and 3) the accumulation of NEFAs is a sensitive marker for myocardial cell damage.

Animals↗

Accurate noninvasive method to diagnose minor atherosclerotic lesions in carotid artery bulb.

In a prospective study using a multigate pulsed Doppler system, minor (less than 30% diameter reduction) carotid artery lesions were diagnosed by detecting not only abnormalities in the blood flow pattern, but also local changes in artery wall distensibility. For the diagnosis of more severe lesions, additional information was obtained from disturbances in the Doppler audio spectrum. Biplane arteriography was used as a reference. The observed agreement, sensitivity, and specificity were 86.6%, 90.3%, and 88.6%, respectively, for all lesions and 85.7%, 82.1%, and 88.6%, respectively, when only minor lesions were considered. kappa (a chance-corrected measure of agreement) was 81.7%. If only blood flow abnormalities were used to detect minor lesions, 43.5% would be missed. Our results indicate that minor carotid artery lesions can be diagnosed noninvasively more accurately when both local blood flow irregularities and local changes in vessel wall distensibility are taken into account.

Adult↗

Ketanserin in the treatment of systemic hypertension during and following coronary artery bypass surgery.

One of the most important problems during cardiac surgery is the prevention and treatment of hypertension, occurring in 40-60% of the patients following coronary artery bypass surgery (CABS). Hypertension should be avoided to prevent myocardial damage, neurologic complications, increased blood loss, and premature graft closure due to intimal damage. During and following cardiac surgery hypertension is routinely treated with vasodilating agents, which generally induce reflex tachycardia and increased intrapulmonary shunting. The results obtained with ketanserin, a specific S2-serotonergic receptor blocker with alpha 1-adrenergic receptor blocking properties, in the prevention and treatment of hypertension in patients undergoing cardiac surgery, are presented. Ketanserin effectively lowers blood pressure by decreasing systemic vascular resistance but does not completely prevent perioperative and postoperative hypertension when administered as a continuous infusion from the start of anesthesia. In contrast to sodium nitroprusside, ketanserin does not induce reflex tachycardia in the treatment of postoperative systemic hypertension following CABS. The compound improves diuresis and perfusion of the skin perioperatively. Ketanserin is devoid of rebound phenomena after its administration is stopped. It is postulated that the antihypertensive effect of ketanserin can be explained by its property of simultaneously blocking alpha 1-adrenergic and S2-serotonergic receptors.

Blood Pressure↗

Formation of multilamellar vesicles by addition of tannic acid to phosphatidylcholine-containing small unilamellar vesicles.

Tannic acid induces aggregation and formation of multilamellar vesicles when added to preparations of small unilamellar vesicles, specifically those containing phosphatidylcholine. Aggregation and clustering of vesicles was demonstrated by cryo-electron microscopy of thin films and by freeze-fracture technique. Turbidity measurements revealed an approximately one-to-one molar ratio between tannic acid and phosphatidylcholine necessary for a fast and massive aggregation of the small unilamellar vesicles. When tannic acid-induced aggregates were dehydrated and embedded for conventional thin-section electron microscopy, multilamellar vesicles were retrieved in thin sections. It is concluded from morphological studies, as well as previous tracer studies, that tannic acid, at least to a great extent, prevents the extraction of phosphatidylcholine. Multilamellar vesicles were also observed in tannic acid-treated vesicles prepared from total lipid extracts from either rabbit or rat hearts. Substantially more multilamellar vesicles were retrieved in the rabbit vesicle preparation. This difference can probably be explained by the difference in the proportion of the plasmalogen phosphatidylcholine, and possibly the content of sphingomyelin, in lipid extracts of rabbit and rat hearts. It is concluded that the dual effect (reduced extraction and aggregation) of tannic acid on phosphatidylcholines should be taken into consideration when tannic acid is used in tissue preparation.

Animals↗

Noninvasive assessment of artery wall properties in children aged 4-19 years.

The vessel wall properties of the common carotid artery were noninvasively studied in 53 normotensive, presumed normal boys of various ages (4-19 yr) with the use of a multigate pulsed Doppler system. This device allows the on-line recording of velocity profiles and the relative changes in carotid artery diameter during the cardiac cycle. From the width of these profiles, the internal diameter of the carotid artery can be determined. With the use of internal carotid artery diameter, relative changes in carotid artery diameter during the cardiac cycle, and pulse pressure the pulse pressure, as measured in the brachial artery, the distensibility coefficient and the cross-sectional compliance were calculated. The children were allotted to three different age groups: group I (4-10 yr), group II (11-14 yr), and group III (15-19 yr). In the older children (group III) the systolic arterial pressure and the pulse pressure were significantly higher than in groups I and II. The carotid artery diameter was significantly larger and the distensibility coefficient was significantly smaller in group III than in groups I and II. The cross-sectional compliance was not significantly different in the age groups, which can be explained by the larger artery diameter in the older age group. The findings indicate that the carotid artery wall is less distensible in adolescents than in younger children. The subjects in group III showed similar carotid artery wall properties as the young adults (aged 20-34 yr) in a previous study. Therefore, it is likely that in adolescents the vascular system can be considered as mature as far as the arterial wall properties are concerned.

Adolescent↗